Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0008284 positive regulation of cell population proliferation	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0030335 positive regulation of cell migration	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of cell migration is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0001525 angiogenesis	IBA GO_REF:0000033	ACCEPT	Summary: Angiogenesis is supported as an important PDGFA-associated tissue process. Reason: PDGF-A/PDGFR signaling supports local mesenchymal and neurovascular behaviors relevant to angiogenesis and vascular stability. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md In a 2024 oxygen-induced retinopathy (OIR) mouse model, retinal PDGF-A overexpression increased astrocyte-associated markers (e.g., GFAP, Pax2), increased PDGFRα expression in astrocyte-rich regions, increased vascular density, and reduced the area of vascular regression immediately after hyperoxic exposure—supporting a role for PDGF-A/PDGFRα signaling in astrocyte support and neurovascular stability under hyperoxic stress.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a supported downstream PDGFR signaling output. Reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of receptor autophosphorylation. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output.
GO:0048008 platelet-derived growth factor receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: platelet-derived growth factor receptor signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0005161 platelet-derived growth factor receptor binding	IBA GO_REF:0000033	ACCEPT	Summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0005615 extracellular space	IBA GO_REF:0000033	ACCEPT	Summary: extracellular space is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of ERK1 and ERK2 cascade is a supported downstream PDGFR signaling output. Reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of receptor autophosphorylation. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output.
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0008083 growth factor activity	IEA GO_REF:0000120	ACCEPT	Summary: growth factor activity is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000117	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0048018 receptor ligand activity	IEA GO_REF:0000117	ACCEPT	Summary: receptor ligand activity is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0051781 positive regulation of cell division	IEA GO_REF:0000043	ACCEPT	Summary: positive regulation of cell division is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	MARK AS OVER ANNOTATED	Summary: Protein binding is supported only as a generic description of more specific PDGF receptor and dimer interactions. Reason: The informative molecular functions are PDGF receptor binding/receptor ligand activity and PDGF dimerization, not generic protein binding. Proposed replacements: platelet-derived growth factor receptor binding receptor ligand activity Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB).
GO:0005515 protein binding	IPI PMID:7679113 Mechanism of platelet-derived growth factor (PDGF) AA, AB, a...	MARK AS OVER ANNOTATED	Summary: Protein binding is supported only as a generic description of more specific PDGF receptor and dimer interactions. Reason: The informative molecular functions are PDGF receptor binding/receptor ligand activity and PDGF dimerization, not generic protein binding. Proposed replacements: platelet-derived growth factor receptor binding receptor ligand activity Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB).
GO:0005615 extracellular space	IEA GO_REF:0000107	ACCEPT	Summary: extracellular space is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005902 microvillus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Microvillus localization is not supported by the PDGFA evidence and is likely over-specific for this secreted/pericellular ligand. Reason: The Falcon synthesis supports extracellular, pericellular, and secretory-pathway contexts, but does not provide evidence that microvillus is an informative PDGFA localization. Proposed replacements: extracellular space extracellular region Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells.
GO:0048565 digestive tract development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: digestive tract development is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:1990401 embryonic lung development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: embryonic lung development is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0035790 platelet-derived growth factor receptor-alpha signaling pathway	NAS PMID:11297552 Platelet-derived growth factor C (PDGF-C), a novel growth fa...	ACCEPT	Summary: platelet-derived growth factor receptor-alpha signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0038083 peptidyl-tyrosine autophosphorylation	NAS PMID:11297552 Platelet-derived growth factor C (PDGF-C), a novel growth fa...	REMOVE	Summary: Peptidyl-tyrosine autophosphorylation is receptor biology, not a process carried out by PDGFA. Reason: PDGF-A ligand binding induces PDGFR autophosphorylation, but PDGFA itself is not a kinase and does not catalyze or autophosphorylate proteins. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0048008 platelet-derived growth factor receptor signaling pathway	NAS PMID:7679113 Mechanism of platelet-derived growth factor (PDGF) AA, AB, a...	ACCEPT	Summary: platelet-derived growth factor receptor signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0035790 platelet-derived growth factor receptor-alpha signaling pathway	NAS PMID:7679113 Mechanism of platelet-derived growth factor (PDGF) AA, AB, a...	ACCEPT	Summary: platelet-derived growth factor receptor-alpha signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:10806482 PDGF-C is a new protease-activated ligand for the PDGF alpha...	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:2439522 PDGF induces c-myc mRNA expression in MG-63 human osteosarco...	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-186785	KEEP AS NON CORE	Summary: Golgi lumen is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-8865276	KEEP AS NON CORE	Summary: Golgi lumen is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005161 platelet-derived growth factor receptor binding	IDA PMID:2439522 PDGF induces c-myc mRNA expression in MG-63 human osteosarco...	ACCEPT	Summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:1990401 embryonic lung development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: embryonic lung development is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0008083 growth factor activity	IDA PMID:12070119 Adipocyte-derived plasma protein adiponectin acts as a plate...	ACCEPT	Summary: growth factor activity is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0009986 cell surface	IDA PMID:2538439 Collagen-induced binding to human platelets of platelet-deri...	ACCEPT	Summary: cell surface is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-186785	KEEP AS NON CORE	Summary: Golgi membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-382053	KEEP AS NON CORE	Summary: Golgi membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-1524182	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-1524186	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186765	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186773	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186778	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186780	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186785	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186800	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186819	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186826	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-186834	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-2316434	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-2400009	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-380780	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-380782	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-382052	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-382054	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-382055	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-382056	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-382058	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-389083	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-481007	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-5672965	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-9674093	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005788 endoplasmic reticulum lumen	TAS Reactome:R-HSA-382053	KEEP AS NON CORE	Summary: endoplasmic reticulum lumen is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0031093 platelet alpha granule lumen	TAS Reactome:R-HSA-481007	KEEP AS NON CORE	Summary: platelet alpha granule lumen is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-8865276	KEEP AS NON CORE	Summary: Golgi membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not the principal site of action. Reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-2396337	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-389086	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-8864036	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-8865276	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0005576 extracellular region	TAS Reactome:R-HSA-9796072	ACCEPT	Summary: extracellular region is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0035793 positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	IDA PMID:19019919 PDGF receptor-{beta} modulates metanephric mesenchyme chemot...	KEEP AS NON CORE	Summary: positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0001525 angiogenesis	ISS GO_REF:0000024	ACCEPT	Summary: Angiogenesis is supported as an important PDGFA-associated tissue process. Reason: PDGF-A/PDGFR signaling supports local mesenchymal and neurovascular behaviors relevant to angiogenesis and vascular stability. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md In a 2024 oxygen-induced retinopathy (OIR) mouse model, retinal PDGF-A overexpression increased astrocyte-associated markers (e.g., GFAP, Pax2), increased PDGFRα expression in astrocyte-rich regions, increased vascular density, and reduced the area of vascular regression immediately after hyperoxic exposure—supporting a role for PDGF-A/PDGFRα signaling in astrocyte support and neurovascular stability under hyperoxic stress.
GO:0001942 hair follicle development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: hair follicle development is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0002053 positive regulation of mesenchymal cell proliferation	ISS GO_REF:0000024	ACCEPT	Summary: positive regulation of mesenchymal cell proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0005902 microvillus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Microvillus localization is not supported by the PDGFA evidence and is likely over-specific for this secreted/pericellular ligand. Reason: The Falcon synthesis supports extracellular, pericellular, and secretory-pathway contexts, but does not provide evidence that microvillus is an informative PDGFA localization. Proposed replacements: extracellular space extracellular region Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells.
GO:0009887 animal organ morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: animal organ morphogenesis is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0030031 cell projection assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: cell projection assembly is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0030036 actin cytoskeleton organization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: actin cytoskeleton organization is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0043588 skin development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: skin development is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0048286 lung alveolus development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: lung alveolus development is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0060683 regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0030335 positive regulation of cell migration	IDA PMID:11788434 Effect of platelet-derived growth factor isoforms in rat met...	ACCEPT	Summary: positive regulation of cell migration is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0043410 positive regulation of MAPK cascade	IMP PMID:11788434 Effect of platelet-derived growth factor isoforms in rat met...	ACCEPT	Summary: positive regulation of MAPK cascade is a supported downstream PDGFR signaling output. Reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of receptor autophosphorylation. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA PMID:11788434 Effect of platelet-derived growth factor isoforms in rat met...	ACCEPT	Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a supported downstream PDGFR signaling output. Reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of receptor autophosphorylation. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA PMID:19019919 PDGF receptor-{beta} modulates metanephric mesenchyme chemot...	ACCEPT	Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is a supported downstream PDGFR signaling output. Reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of receptor autophosphorylation. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output.
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IDA PMID:11788434 Effect of platelet-derived growth factor isoforms in rat met...	ACCEPT	Summary: positive regulation of ERK1 and ERK2 cascade is a supported downstream PDGFR signaling output. Reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of receptor autophosphorylation. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output.
GO:0072124 regulation of glomerular mesangial cell proliferation	IDA NOT PMID:11788434 Effect of platelet-derived growth factor isoforms in rat met...	ACCEPT	Summary: Negated annotation: the cited metanephric mesenchymal-cell study found that PDGF-A/PDGF-AA did not drive the mesangial-cell proliferative response measured through DNA synthesis. Reason: This NOT annotation should be retained because the cited experiment supports absence of this PDGFA proliferative response in the tested metanephric mesenchyme context. Supporting Evidence: PMID:11788434 PDGF AA caused modest cell migration but had no effect on DNA synthesis, unlike PDGF BB, which potently stimulated migration and DNA synthesis.
GO:2000278 regulation of DNA biosynthetic process	IDA NOT PMID:11788434 Effect of platelet-derived growth factor isoforms in rat met...	ACCEPT	Summary: Negated annotation: this row should not be read as a positive DNA-synthesis function; PDGF-A/PDGF-AA lacked the cited metanephric mesenchyme response, with the clearest DNA-synthesis support coming from the paired PMID:11788434 evidence. Reason: The annotation is a NOT assertion and should be retained, but the PMID:19019919 abstract supports absence of a PDGF-AA response in this context rather than a positive non-core function. Supporting Evidence: PMID:11788434 PDGF AA caused modest cell migration but had no effect on DNA synthesis, unlike PDGF BB, which potently stimulated migration and DNA synthesis.
GO:2000278 regulation of DNA biosynthetic process	IDA NOT PMID:19019919 PDGF receptor-{beta} modulates metanephric mesenchyme chemot...	ACCEPT	Summary: Negated annotation: the cited metanephric mesenchyme evidence indicates that PDGF-A/PDGF-AA did not stimulate the DNA-synthesis response in the tested context. Reason: The annotation is a NOT assertion and should be retained as evidence that PDGFA lacks this DNA-biosynthetic/mitogenic effect in those experiments, rather than described as a positive non-core function. Supporting Evidence: PMID:19019919 PDGF BB stimulated cell migration in +/+ cells, whereas PDGF AA did not. PMID:11788434 PDGF AA caused modest cell migration but had no effect on DNA synthesis, unlike PDGF BB, which potently stimulated migration and DNA synthesis.
GO:0005518 collagen binding	IDA PMID:8900172 Type I, II, III, IV, V, and VI collagens serve as extracellu...	KEEP AS NON CORE	Summary: Collagen/ECM binding is consistent with extracellular matrix-associated PDGF-A localization but is not the core ligand activity. Reason: PDGF-A spatial range is shaped by extracellular/pericellular retention; receptor binding remains the core molecular function. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.” file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells.
GO:0014910 regulation of smooth muscle cell migration	IDA PMID:9409235 Platelet-derived growth factor beta-receptors can both promo...	ACCEPT	Summary: regulation of smooth muscle cell migration is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0050919 negative chemotaxis	IDA PMID:9409235 Platelet-derived growth factor beta-receptors can both promo...	KEEP AS NON CORE	Summary: negative chemotaxis is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0001775 cell activation	TAS PMID:10508235 Mechanism of action and in vivo role of platelet-derived gro...	KEEP AS NON CORE	Summary: cell activation is plausible downstream PDGFA biology but secondary to the core receptor-ligand signaling function. Reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect context-specific consequences of PDGF-A/PDGFR signaling. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors.
GO:0005161 platelet-derived growth factor receptor binding	IPI PMID:2536956 Isolation of a novel receptor cDNA establishes the existence...	ACCEPT	Summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:17470632 Vascular endothelial growth factor can signal through platel...	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0030335 positive regulation of cell migration	IDA PMID:17470632 Vascular endothelial growth factor can signal through platel...	ACCEPT	Summary: positive regulation of cell migration is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0032956 regulation of actin cytoskeleton organization	TAS PMID:10508235 Mechanism of action and in vivo role of platelet-derived gro...	KEEP AS NON CORE	Summary: regulation of actin cytoskeleton organization is secondary to PDGFA secreted receptor-ligand signaling. Reason: The core PDGFA function is extracellular PDGF receptor ligand activity. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0042060 wound healing	TAS PMID:10508235 Mechanism of action and in vivo role of platelet-derived gro...	ACCEPT	Summary: wound healing is a supported tissue-level PDGF pathway role. Reason: PDGF signaling has well-established relevance to wound repair and local mesenchymal responses. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md A widely cited clinical application of the PDGF system is topical PDGF-based therapy for chronic wounds; a large clinical study (>900 patients) is summarized as showing topical PDGF improved healing of chronic full-thickness diabetic foot ulcers. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0048008 platelet-derived growth factor receptor signaling pathway	IDA PMID:2536956 Isolation of a novel receptor cDNA establishes the existence...	ACCEPT	Summary: platelet-derived growth factor receptor signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0048146 positive regulation of fibroblast proliferation	IDA PMID:10806482 PDGF-C is a new protease-activated ligand for the PDGF alpha...	ACCEPT	Summary: positive regulation of fibroblast proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0005161 platelet-derived growth factor receptor binding	IDA PMID:2836953 A common PDGF receptor is activated by homodimeric A and B f...	ACCEPT	Summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular function. Reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes, especially PDGFRα. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0005615 extracellular space	IDA PMID:3754619 cDNA sequence and chromosomal localization of human platelet...	ACCEPT	Summary: extracellular space is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0008284 positive regulation of cell population proliferation	IDA PMID:2836953 A common PDGF receptor is activated by homodimeric A and B f...	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:7073684 Platelet-derived growth factor: identification of constituen...	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0009611 response to wounding	IDA PMID:2538439 Collagen-induced binding to human platelets of platelet-deri...	ACCEPT	Summary: response to wounding is a supported tissue-level PDGF pathway role. Reason: PDGF signaling has well-established relevance to wound repair and local mesenchymal responses. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md A widely cited clinical application of the PDGF system is topical PDGF-based therapy for chronic wounds; a large clinical study (>900 patients) is summarized as showing topical PDGF improved healing of chronic full-thickness diabetic foot ulcers. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0009986 cell surface	IDA PMID:2836953 A common PDGF receptor is activated by homodimeric A and B f...	ACCEPT	Summary: cell surface is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0009986 cell surface	IDA PMID:291037 Platelet-derived growth factor: purification and partial cha...	ACCEPT	Summary: cell surface is consistent with secreted, extracellular, and pericellular PDGF-A ligand action. Reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface receptor-bearing cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. file:human/PDGFA/PDGFA-deep-research-falcon.md A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.”
GO:0010512 negative regulation of phosphatidylinositol biosynthetic process	IDA PMID:2538439 Collagen-induced binding to human platelets of platelet-deri...	KEEP AS NON CORE	Summary: negative regulation of phosphatidylinositol biosynthetic process is supported by older platelet-response evidence but is not a core PDGFA function. Reason: This platelet-feedback biology is secondary to the main secreted growth-factor ligand role. Supporting Evidence: PMID:2538439 Platelet-derived growth factor (PDGF) is known to inhibit collagen-induced platelet aggregation. PMID:2538439 These results suggest that (i) a specific PDGF receptor can be induced by collagen, and (ii) PDGF can effect the early events of collagen-induced platelet activation by inhibiting PIP2 resynthesis and P43 and P20 phosphorylation.
GO:0010544 negative regulation of platelet activation	IDA PMID:2538439 Collagen-induced binding to human platelets of platelet-deri...	KEEP AS NON CORE	Summary: negative regulation of platelet activation is supported by older platelet-response evidence but is not a core PDGFA function. Reason: This platelet-feedback biology is secondary to the main secreted growth-factor ligand role. Supporting Evidence: PMID:2538439 Platelet-derived growth factor (PDGF) is known to inhibit collagen-induced platelet aggregation. PMID:2538439 These results suggest that (i) a specific PDGF receptor can be induced by collagen, and (ii) PDGF can effect the early events of collagen-induced platelet activation by inhibiting PIP2 resynthesis and P43 and P20 phosphorylation.
GO:0042803 protein homodimerization activity	IDA PMID:2836953 A common PDGF receptor is activated by homodimeric A and B f...	ACCEPT	Summary: protein homodimerization activity is consistent with PDGF-A dimeric ligand assembly. Reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are the signaling ligand forms. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB). file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs are secreted growth factors that function as disulfide-linked dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFA contributes the A-chain, which most commonly forms the PDGF-AA homodimer; PDGF-AB has been detected in human platelets.
GO:0042803 protein homodimerization activity	IDA PMID:3754619 cDNA sequence and chromosomal localization of human platelet...	ACCEPT	Summary: protein homodimerization activity is consistent with PDGF-A dimeric ligand assembly. Reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are the signaling ligand forms. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB). file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs are secreted growth factors that function as disulfide-linked dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFA contributes the A-chain, which most commonly forms the PDGF-AA homodimer; PDGF-AB has been detected in human platelets.
GO:0046982 protein heterodimerization activity	IPI PMID:7073684 Platelet-derived growth factor: identification of constituen...	ACCEPT	Summary: protein heterodimerization activity is consistent with PDGF-A dimeric ligand assembly. Reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are the signaling ligand forms. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB). file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs are secreted growth factors that function as disulfide-linked dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFA contributes the A-chain, which most commonly forms the PDGF-AA homodimer; PDGF-AB has been detected in human platelets.
GO:0048008 platelet-derived growth factor receptor signaling pathway	IDA PMID:2439522 PDGF induces c-myc mRNA expression in MG-63 human osteosarco...	ACCEPT	Summary: platelet-derived growth factor receptor signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0048008 platelet-derived growth factor receptor signaling pathway	IDA PMID:2836953 A common PDGF receptor is activated by homodimeric A and B f...	ACCEPT	Summary: platelet-derived growth factor receptor signaling pathway is the core receptor-signaling pathway for PDGFA. Reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling most central. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins.
GO:0048146 positive regulation of fibroblast proliferation	IDA PMID:2439522 PDGF induces c-myc mRNA expression in MG-63 human osteosarco...	ACCEPT	Summary: positive regulation of fibroblast proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0048407 platelet-derived growth factor binding	IPI PMID:7073684 Platelet-derived growth factor: identification of constituen...	ACCEPT	Summary: platelet-derived growth factor binding is consistent with PDGF-A dimeric ligand assembly. Reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are the signaling ligand forms. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB). file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs are secreted growth factors that function as disulfide-linked dimers. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFA contributes the A-chain, which most commonly forms the PDGF-AA homodimer; PDGF-AB has been detected in human platelets.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:16462734 VEGF-C is a trophic factor for neural progenitors in the ver...	ACCEPT	Summary: positive regulation of cell population proliferation is a supported cellular response to PDGFA growth-factor signaling. Reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central PDGF-A/PDGFR biological outputs. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. file:human/PDGFA/PDGFA-deep-research-falcon.md Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair.
GO:0007267 cell-cell signaling	TAS PMID:2842868 Comparison of biological properties and transforming potenti...	ACCEPT	Summary: Cell-cell signaling captures the paracrine signaling nature of PDGFA. Reason: PDGF-A is a local extracellular/paracrine ligand acting between source and PDGFR-expressing target cells. Supporting Evidence: file:human/PDGFA/PDGFA-deep-research-falcon.md PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. file:human/PDGFA/PDGFA-deep-research-falcon.md Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells.

Core Functions

Secreted dimeric PDGF-A receptor ligand activity, mainly as PDGF-AA, activating PDGFR-alpha-biased receptor signaling in the extracellular/pericellular microenvironment.

Molecular Function:

platelet-derived growth factor receptor binding

Directly Involved In:

platelet-derived growth factor receptor signaling pathway positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of ERK1 and ERK2 cascade positive regulation of cell population proliferation positive regulation of cell migration

Cellular Locations:

extracellular region cell surface

Supporting Evidence:

file:human/PDGFA/PDGFA-deep-research-falcon.md
The UniProt accession **P04085** corresponds to human **PDGFA** encoding **platelet-derived growth factor subunit A (PDGF-A chain)**, a secreted **PDGF/VEGF-family cystine-knot growth factor** produced as a **precursor** and functioning as a **disulfide-linked dimeric ligand** (commonly **PDGF-AA**, also **PDGF-AB**).
file:human/PDGFA/PDGFA-deep-research-falcon.md
**PDGFA** contributes the **A-chain**, which most commonly forms the **PDGF-AA homodimer**; **PDGF-AB** has been detected in human platelets.
file:human/PDGFA/PDGFA-deep-research-falcon.md
A key specificity for PDGFA biology is that **PDGF-AA preferentially induces PDGFRα homodimers**, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers.
file:human/PDGFA/PDGFA-deep-research-falcon.md
PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**: it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.
file:human/PDGFA/PDGFA-deep-research-falcon.md
Because PDGF-A is secreted and can be **pericellular ECM-bound** or **soluble** depending on splice isoform, its principal site of action is the **extracellular space** in the local tissue microenvironment, acting on **cell-surface PDGFRα/β** on neighboring responsive cells.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10508235

Mechanism of action and in vivo role of platelet-derived growth factor.

PMID:10806482

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

PMID:11297552

Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor.

PMID:11788434

Effect of platelet-derived growth factor isoforms in rat metanephric mesenchymal cells.

PMID:12070119

Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell.

PMID:16462734

VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain.

PMID:17470632

Vascular endothelial growth factor can signal through platelet-derived growth factor receptors.

PMID:19019919

PDGF receptor-{beta} modulates metanephric mesenchyme chemotaxis induced by PDGF AA.

PMID:2439522

PDGF induces c-myc mRNA expression in MG-63 human osteosarcoma cells but does not stimulate cell replication.

PMID:25241761

Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.

PMID:2536956

Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes.

PMID:2538439

Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation.

PMID:2836953

A common PDGF receptor is activated by homodimeric A and B forms of PDGF.

PMID:2842868

Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains.

PMID:291037

Platelet-derived growth factor: purification and partial characterization.

PMID:3754619

cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines.

PMID:7073684

Platelet-derived growth factor: identification of constituent polypeptide chains.

PMID:7679113

Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor.

PMID:8900172

Type I, II, III, IV, V, and VI collagens serve as extracellular ligands for the isoforms of platelet-derived growth factor (AA, BB, and AB).

PMID:9409235

Platelet-derived growth factor beta-receptors can both promote and inhibit chemotaxis in human vascular smooth muscle cells.

Reactome:R-HSA-1524182

Activated PLC gamma dissociates from the PDGF receptor

Reactome:R-HSA-1524186

Phosphorylation of PLCgamma by PDGFR

Reactome:R-HSA-186765

PLC-gamma binds to the active receptor

Reactome:R-HSA-186773

PDGF dimer binds two receptors simultaneously

Reactome:R-HSA-186778

SHP2 binds to the active receptor

Reactome:R-HSA-186780

PI3-kinase binds to the active receptor

Reactome:R-HSA-186785

PDGF-AA clevage by Furin

Reactome:R-HSA-186800

PI3K catalyses the phosphorylation of PIP2 to PIP3

Reactome:R-HSA-186819

SH2 domain of Src binds to the active receptor

Reactome:R-HSA-186826

GRB2:SOS1 complex binds to the active receptor

Reactome:R-HSA-186834

SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)

Reactome:R-HSA-2316434

PI3K phosphorylates PIP2 to PIP3

Reactome:R-HSA-2396337

HSPG2 binds FGF2(10-155), Fibronectn matrix, Transthyretin tetramer, PDGFA homodimer, PDGFB homodimer

Reactome:R-HSA-2400009

PI3K inhibitors block PI3K catalytic activity

Reactome:R-HSA-380780

TODO: Fetch title

Reactome:R-HSA-380782

STAT binds to the active receptor

Reactome:R-HSA-382052

p130Cas and C3G bind PDGFR bound Crk

Reactome:R-HSA-382053

TODO: Fetch title

Reactome:R-HSA-382054

PDGF binds to extracellular matrix proteins

Reactome:R-HSA-382055

Grb7 binds to the active PDGF receptor

Reactome:R-HSA-382056

Crk binds to the active PDGF receptor

Reactome:R-HSA-382058

Nck binds to the active PDGF receptor

Reactome:R-HSA-389083

Autophosphorylation of PDGF alpha receptors

Reactome:R-HSA-389086

Autophosphorylation of PDGF alpha/beta receptors

Reactome:R-HSA-481007

Exocytosis of platelet alpha granule contents

Reactome:R-HSA-5672965

RAS GEFs promote RAS nucleotide exchange

Reactome:R-HSA-8864036

PTPN12 dephosphorylates PDGFRB at Y1021

Reactome:R-HSA-8865276

PDGF-AB clevage by Furin

Reactome:R-HSA-9674093

PDGFRs bind type I TKI

Reactome:R-HSA-9796072

NFE2L2 dependent PDGFA expression

file:human/PDGFA/PDGFA-deep-research-falcon.md

Falcon deep research synthesis for PDGFA

Deep Research

Falcon

(PDGFA-deep-research-falcon.md)

Research report: Human **PDGFA** (UniProt **P04085**) – functional annotation Falcon Edison Scientific Literature 28 citations 2026-05-12T02:13:01.787247

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human PDGFA (UniProt P04085) – functional annotation

0) Target verification (gene/protein identity)

The UniProt accession P04085 corresponds to human PDGFA encoding platelet-derived growth factor subunit A (PDGF-A chain), a secreted PDGF/VEGF-family cystine-knot growth factor produced as a precursor and functioning as a disulfide-linked dimeric ligand (commonly PDGF-AA, also PDGF-AB). These properties and naming are consistent across authoritative reviews and recent literature. (andrae2008roleofplateletderived pages 1-2, basciani2010roleofplateletderived pages 3-5, strell2024functionalandclinical pages 1-3)

1) Key concepts, definitions, and current understanding

1.1 PDGF ligands and dimerization nomenclature

PDGFs are secreted growth factors that function as disulfide-linked dimers. The classical PDGF system comprises five dimeric ligands (PDGF-AA, -AB, -BB, -CC, -DD) assembled from four gene products (PDGF-A, -B, -C, -D). (ma2024targetingpdgfpdgfrsignaling pages 1-2)

PDGFA contributes the A-chain, which most commonly forms the PDGF-AA homodimer; PDGF-AB has been detected in human platelets. (andrae2008roleofplateletderived pages 1-2)

1.2 Receptor system and ligand–receptor specificity

PDGFs signal through two receptor tyrosine kinases, PDGFRα and PDGFRβ. Ligand binding induces receptor dimerization and autophosphorylation of intracellular tyrosines, generating docking sites for downstream signaling proteins. (strell2024functionalandclinical pages 1-3, andrae2008roleofplateletderived pages 2-4)

A key specificity for PDGFA biology is that PDGF-AA preferentially induces PDGFRα homodimers, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased toward PDGFRβ-containing dimers. (strell2024functionalandclinical pages 1-3)

1.3 PDGFA is a signaling ligand (not an enzyme)

PDGF-A’s “primary function” in functional-annotation terms is paracrine signaling: it acts as an extracellular ligand that activates PDGFRα (primarily) on target cells to regulate proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors. (strell2024functionalandclinical pages 1-3, andrae2008roleofplateletderived pages 1-2)

2) Molecular biology of PDGFA protein: synthesis, processing, and localization

2.1 Biosynthesis and proteolytic maturation

PDGF-A (and PDGF-B) are synthesized as disulfide-linked propeptide dimers and require intracellular N-terminal prodomain removal by furin or related proprotein convertases during trafficking through the secretory pathway. N-terminal processing is described as necessary for PDGF-A to acquire receptor-binding activity. (appelmann2010angiogenesisinhibitionin pages 11-14, andrae2008roleofplateletderived pages 2-4)

An Endocrine Reviews synthesis similarly notes that PDGF-A/-B contain an amino-terminal prodomain cleaved intracellularly when secreted, and also highlights intracellular processing steps enabling receptor-binding competence. (basciani2010roleofplateletderived pages 3-5)

2.2 Alternative splicing and extracellular matrix (ECM)/pericellular retention

A distinctive functional feature of PDGF-A is that alternative splicing generates isoforms with or without a basic C-terminal “retention motif.” The long splice form contains the retention motif and tends to remain cell-associated/pericellular (including ECM/basement membrane association), whereas the isoform lacking this motif is more diffusible/soluble. (andrae2008roleofplateletderived pages 5-6, basciani2010roleofplateletderived pages 3-5, strell2024functionalandclinical pages 1-3)

Mechanistically, this retention motif mediates electrostatic interactions with ECM components (commonly discussed in the context of heparan sulfate proteoglycans and related ECM binding). (basciani2010roleofplateletderived pages 3-5, appelmann2010angiogenesisinhibitionin pages 11-14)

2.3 Where PDGFA acts (cellular/extracellular localization)

Because PDGF-A is secreted and can be pericellular ECM-bound or soluble depending on splice isoform, its principal site of action is the extracellular space in the local tissue microenvironment, acting on cell-surface PDGFRα/β on neighboring responsive cells. (andrae2008roleofplateletderived pages 5-6, strell2024functionalandclinical pages 1-3)

3) Signaling pathways downstream of PDGF-AA/PDGFRα

3.1 Canonical signaling modules

Upon receptor activation, phosphorylated PDGFR tyrosines recruit SH2-domain-containing proteins. Reported signaling components and pathways include:
- RAS–MAPK module (e.g., via Grb2/Shc/Sos → Ras → Raf-1 → MAPK cascade), promoting transcriptional responses supporting growth, differentiation, and migration. (appelmann2010angiogenesisinhibitionin pages 14-16, andrae2008roleofplateletderived pages 5-6)
- PI3K signaling, with effectors including Akt/PKB, linked to cytoskeletal remodeling, migration, growth, and survival. (appelmann2010angiogenesisinhibitionin pages 14-16, andrae2008roleofplateletderived pages 5-6)
- PLCγ phosphorylation, leading to Ca2+ mobilization and PKC activation. (appelmann2010angiogenesisinhibitionin pages 14-16, andrae2008roleofplateletderived pages 5-6)
- STAT-family docking/activation is included among PDGFR-associated effectors in a recent tumor-stroma focused review. (strell2024functionalandclinical pages 1-3)

3.2 Recent mechanistic advance (2024): coupling to alternative splicing and endosomal signaling

A notable 2024 mechanistic study connects PDGF-AA/PDGFRα signaling to RNA-binding and alternative splicing control. In mouse embryonic palatal mesenchyme cells, PI3K/Akt downstream of PDGFRα phosphorylates the splicing factor Srsf3, driving its nuclear translocation. PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing of transcripts involved in PI3K signaling and endosomal trafficking; Srsf3 activity in this context contributes to retention of PDGFRα in early endosomes and amplifies PI3K-mediated Akt signaling, linking receptor trafficking to signaling output. (forman2024pdgfrαsignalingregulates pages 1-2, forman2024pdgfrαsignalingregulates pages 10-13)

4) Physiological roles and biological processes (focused functional annotation)

4.1 Core biological role: local mesenchymal regulation

Across authoritative syntheses, PDGF ligands (including PDGF-AA) are emphasized as local/paracrine factors that regulate mesenchymal cell behaviors (proliferation, chemotaxis, matrix contraction) in development and tissue maintenance/repair. (strell2024functionalandclinical pages 1-3, andrae2008roleofplateletderived pages 1-2)

4.2 Neurovascular unit / retina (2024)

In a 2024 oxygen-induced retinopathy (OIR) mouse model, retinal PDGF-A overexpression increased astrocyte-associated markers (e.g., GFAP, Pax2), increased PDGFRα expression in astrocyte-rich regions, increased vascular density, and reduced the area of vascular regression immediately after hyperoxic exposure—supporting a role for PDGF-A/PDGFRα signaling in astrocyte support and neurovascular stability under hyperoxic stress. (yokota2024plateletderivedgrowthfactor pages 7-9, yokota2024plateletderivedgrowthfactor pages 9-11)

4.3 Developmental craniofacial context (2024)

PDGFRα signaling is a major driver of craniofacial development, and the 2024 splicing/endosomal study provides mechanistic detail for how PDGF-AA/PDGFRα can program gene expression outputs through Akt→Srsf3 and alternative splicing, with neural crest Srsf3 disruption leading to severe midline facial clefting. (forman2024pdgfrαsignalingregulates pages 1-2)

5) Disease associations and clinical relevance

5.1 Fibrosis and stromal remodeling

Recent synthesis emphasizing stromal PDGFR roles highlights that dysregulated PDGFRα signaling is linked to fibrotic pathologies (e.g., pulmonary/dermal fibrosis) and other tissue remodeling contexts, consistent with PDGF-AA/PDGFRα being a potent pro-mesenchymal signal that can promote matrix remodeling when overactive. (strell2024functionalandclinical pages 1-3)

5.2 Tumor microenvironment (2024 review perspective)

A 2024 Cancer Metastasis Reviews article argues that PDGF signaling in stromal/mesenchymal cells is clinically relevant across cancers (tumor growth, metastasis, drug efficacy), and highlights inter-patient variability in stromal PDGFR expression as a rationale for stratified approaches and biomarker development. (strell2024functionalandclinical pages 1-3)

5.3 Structured database evidence (Open Targets)

Open Targets identifies PDGFA as associated with multiple disease concepts, including androgenetic alopecia, Dupuytren contracture / palmar fibromatosis, and cancer, with multiple literature-linked evidences (evidence counts shown in the Open Targets output). (OpenTargets Search: -PDGFA)

6) Current applications and real-world implementations

6.1 Therapeutic strategies targeting the PDGF/PDGFR axis

Clinical strategies commonly target the PDGF system indirectly via PDGFR tyrosine kinase inhibition (often as part of multi-kinase anti-angiogenic regimens). The therapeutic rationale is to blunt PDGFR-driven stromal proliferation/migration, pericyte/stromal support of pathological angiogenesis, and fibrotic remodeling. (strell2024functionalandclinical pages 1-3, appelmann2010angiogenesisinhibitionin pages 11-14)

6.2 Regenerative medicine and wound healing (historical but still clinically informative)

A widely cited clinical application of the PDGF system is topical PDGF-based therapy for chronic wounds; a large clinical study (>900 patients) is summarized as showing topical PDGF improved healing of chronic full-thickness diabetic foot ulcers. (andrae2008roleofplateletderived pages 25-26)

6.3 Emerging/experimental implementation: retinal vascular stabilization

Based on the OIR model, authors propose PDGF-A as a candidate target/strategy for preventing hyperoxia-associated retinal vascular regression (relevant to retinopathy of prematurity), while noting translational caveats and risks of overexpression. (yokota2024plateletderivedgrowthfactor pages 9-11)

7) Expert interpretation and synthesis (authoritative perspectives)

7.1 Spatial control is a defining functional principle for PDGFA

A recurring mechanistic theme is that PDGF-A spatial range is biologically tuned by the presence or absence of a C-terminal retention motif (splice-dependent), providing a plausible explanation for how PDGF-A can mediate strong local effects (pericellular ECM-trapped) versus broader paracrine diffusion (soluble form). This principle is emphasized in authoritative reviews and reiterated in more recent syntheses. (andrae2008roleofplateletderived pages 5-6, strell2024functionalandclinical pages 1-3, basciani2010roleofplateletderived pages 3-5)

7.2 Signaling output depends on receptor trafficking and post-receptor regulation

Beyond canonical kinase cascades, current mechanistic work highlights that PDGFRα signaling is shaped by endosomal residence and receptor trafficking, and can feed back through regulated splicing programs (e.g., Srsf3-dependent) to alter PI3K/endosomal machinery, reinforcing PI3K–Akt output. This provides a modern perspective for functional annotation: PDGF-AA/PDGFRα is not only a mitogenic input but also a systems-level organizer of signaling duration/location and transcript isoform outputs. (forman2024pdgfrαsignalingregulates pages 1-2, forman2024pdgfrαsignalingregulates pages 10-13)

8) Visual evidence: ligand–receptor specificity and signaling overview

The following figures from a 2024 review summarize the PDGF ligand–receptor pairing logic and major downstream effectors (useful for functional annotation and pathway mapping). (strell2024functionalandclinical media f86371c2, strell2024functionalandclinical media 0b99a6a7)

Summary table

Aspect	Key points	Recent (2023-2024) evidence sources	Foundational sources	Notes/quantitative data
Ligand forms	Human PDGFA encodes PDGF-A, a secreted PDGF/VEGF-family cystine-knot ligand that forms disulfide-linked dimers, mainly PDGF-AA and PDGF-AB	Strell 2024; Ma 2024; Yokota 2024 (strell2024functionalandclinical pages 1-3, ma2024targetingpdgfpdgfrsignaling pages 1-2, yokota2024plateletderivedgrowthfactor pages 1-2)	Andrae 2008; Basciani 2010 (andrae2008roleofplateletderived pages 1-2, basciani2010roleofplateletderived pages 3-5)	PDGF-AA is the predominant PDGFA homodimer; PDGF-AB is also recognized in the PDGF system
Processing	PDGF-A is synthesized as a precursor/propeptide dimer and requires intracellular N-terminal prodomain/signal-peptide processing by furin-like convertases to become receptor-competent	Strell 2024 (contextual ligand overview) (strell2024functionalandclinical pages 1-3)	Appelmann 2010; Andrae 2008; Basciani 2010 (appelmann2010angiogenesisinhibitionin pages 11-14, andrae2008roleofplateletderived pages 2-4, basciani2010roleofplateletderived pages 3-5)	Key mechanistic point for functional annotation: PDGFA is a secreted signaling ligand, not an enzyme
ECM retention	Alternative splicing generates PDGF-A isoforms with or without a basic C-terminal retention motif; the long isoform is retained at cell surface/pericellular ECM via electrostatic interactions with heparan sulfate/ECM components, whereas the short isoform is more diffusible	Strell 2024 (strell2024functionalandclinical pages 1-3)	Andrae 2008; Appelmann 2010; Basciani 2010 (andrae2008roleofplateletderived pages 5-6, appelmann2010angiogenesisinhibitionin pages 11-14, basciani2010roleofplateletderived pages 3-5)	ECM retention is central to short-range paracrine signaling and spatial patterning
Receptors	PDGF-AA primarily activates PDGFRα homodimers; PDGF-AB can engage PDGFRα-containing receptor dimers; ligand binding to extracellular Ig-like domains drives receptor dimerization and kinase activation	Strell 2024; Ma 2024; Forman 2024 (strell2024functionalandclinical pages 1-3, ma2024targetingpdgfpdgfrsignaling pages 1-2, forman2024pdgfrαsignalingregulates pages 1-2)	Andrae 2008; Jung 2025 background summary (andrae2008roleofplateletderived pages 2-4, jung2025rolesofpdgfpdgfr pages 1-2)	Canonical target cell context is mesenchymal/mesenchyme-derived PDGFRα-positive cells
Downstream signaling	Activated PDGFRs recruit SH2-domain signaling proteins and stimulate PI3K-AKT, RAS-MAPK/ERK, PLCγ-PKC/Ca2+, and STAT-associated signaling; receptor output is shaped by endocytosis and phosphatases	Forman 2024; Strell 2024; Ma 2024 (forman2024pdgfrαsignalingregulates pages 1-2, forman2024pdgfrαsignalingregulates pages 10-13, strell2024functionalandclinical pages 1-3)	Andrae 2008; Appelmann 2010; Basciani 2010 (andrae2008roleofplateletderived pages 5-6, appelmann2010angiogenesisinhibitionin pages 14-16, basciani2010roleofplateletderived pages 3-5)	Forman 2024 links PDGF-AA/PDGFRα signaling to Srsf3 phosphorylation, alternative splicing, early endosomal retention, and amplified PI3K-AKT signaling
Physiological roles	Core function is local paracrine regulation of proliferation, survival, migration, and mesenchymal-epithelial/neurovascular interactions during development and tissue maintenance; especially important in astrocyte biology, craniofacial development, lung/skin/intestine mesenchyme, and wound repair	Forman 2024; Yokota 2024; Ma 2024 (forman2024pdgfrαsignalingregulates pages 1-2, yokota2024plateletderivedgrowthfactor pages 7-9, ma2024targetingpdgfpdgfrsignaling pages 1-2)	Andrae 2008; Appelmann 2010 (andrae2008roleofplateletderived pages 1-2, appelmann2010angiogenesisinhibitionin pages 11-14)	Yokota 2024 supports a role in retinal neurovascular unit stability under hyperoxia
Disease associations	Dysregulated PDGFA/PDGFRα signaling is implicated in fibrosis, stromal support of tumors, vascular remodeling, BBB dysfunction contexts, and developmental craniofacial defects; database associations also include alopecia/androgenetic alopecia and Dupuytren-related fibromatosis	Strell 2024; Ma 2024; Lv 2024; Forman 2024; OpenTargets (strell2024functionalandclinical pages 1-3, ma2024targetingpdgfpdgfrsignaling pages 1-2, forman2024pdgfrαsignalingregulates pages 1-2, OpenTargets Search: -PDGFA)	Andrae 2008 (andrae2008roleofplateletderived pages 1-2)	OpenTargets shows evidence-backed PDGFA associations with androgenetic alopecia, Dupuytren contracture/palmar fibromatosis, and cancer
Applications/translation	Main translational axis is targeting the PDGF/PDGFR pathway with TKIs in oncology/fibrotic disease, plus regenerative medicine use of PDGF-related growth factor formulations and platelet products; PDGF-A is being explored experimentally for retinal vascular protection and wound-healing signaling	Yokota 2024; Strell 2024; clinical-trials metadata (yokota2024plateletderivedgrowthfactor pages 9-11, strell2024functionalandclinical pages 1-3, OpenTargets Search: -PDGFA)	Andrae 2008 (becaplermin/PDGF pathway history) (andrae2008roleofplateletderived pages 25-26)	Trial landscape includes PDGFR-directed agents such as crenolanib, lucitanib, avapritinib, pazopanib, and lenvatinib; historical wound-healing evidence includes a >900-patient topical PDGF study

Table: This table summarizes the main functional annotation dimensions for human PDGFA, including ligand biology, processing, receptor usage, signaling, roles in physiology and disease, and translational relevance. It is designed as a compact reference to support a longer narrative report.

Key sources (publication date, URL)

Strell C, Rodríguez-Tomàs E, Östman A. Jul 2024. Cancer Metastasis Reviews. https://doi.org/10.1007/s10555-024-10194-7 (strell2024functionalandclinical pages 1-3)
Forman TE et al. Dec 2024. eLife. https://doi.org/10.7554/elife.98531 (forman2024pdgfrαsignalingregulates pages 1-2)
Yokota K et al. Dec 2024. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms252312945 (yokota2024plateletderivedgrowthfactor pages 7-9)
Ma C-N et al. Nov 2024. Biomolecules. https://doi.org/10.3390/biom14111446 (ma2024targetingpdgfpdgfrsignaling pages 1-2)
Andrae J, Gallini R, Betsholtz C. May 2008. Genes & Development. https://doi.org/10.1101/gad.1653708 (andrae2008roleofplateletderived pages 1-2)
Basciani S et al. Dec 2010. Endocrine Reviews. https://doi.org/10.1210/er.2010-0004 (basciani2010roleofplateletderived pages 3-5)
Appelmann I et al. Oct 2010. Recent Results in Cancer Research. https://doi.org/10.1007/978-3-540-78281-0_5 (appelmann2010angiogenesisinhibitionin pages 11-14)
Open Targets Platform (PDGFA disease associations; accessed via tool). (OpenTargets Search: -PDGFA)

References

(andrae2008roleofplateletderived pages 1-2): Johanna Andrae, Radiosa Gallini, and Christer Betsholtz. Role of platelet-derived growth factors in physiology and medicine. Genes & development, 22 10:1276-312, May 2008. URL: https://doi.org/10.1101/gad.1653708, doi:10.1101/gad.1653708. This article has 3233 citations and is from a highest quality peer-reviewed journal.
(basciani2010roleofplateletderived pages 3-5): Sabrina Basciani, Stefania Mariani, Giovanni Spera, and Lucio Gnessi. Role of platelet-derived growth factors in the testis. Endocrine reviews, 31 6:916-39, Dec 2010. URL: https://doi.org/10.1210/er.2010-0004, doi:10.1210/er.2010-0004. This article has 120 citations and is from a domain leading peer-reviewed journal.
(strell2024functionalandclinical pages 1-3): Carina Strell, Elisabet Rodríguez-Tomàs, and Arne Östman. Functional and clinical roles of stromal pdgf receptors in tumor biology. Cancer Metastasis Reviews, 43:1593-1609, Jul 2024. URL: https://doi.org/10.1007/s10555-024-10194-7, doi:10.1007/s10555-024-10194-7. This article has 26 citations.
(ma2024targetingpdgfpdgfrsignaling pages 1-2): Chao-Nan Ma, Shan-Rui Shi, Xue-Ying Zhang, Guo-Song Xin, Xiang Zou, Wen-Lan Li, and Shou-Dong Guo. Targeting pdgf/pdgfr signaling pathway by microrna, lncrna, and circrna for therapy of vascular diseases: a narrow review. Biomolecules, 14:1446, Nov 2024. URL: https://doi.org/10.3390/biom14111446, doi:10.3390/biom14111446. This article has 14 citations.
(andrae2008roleofplateletderived pages 2-4): Johanna Andrae, Radiosa Gallini, and Christer Betsholtz. Role of platelet-derived growth factors in physiology and medicine. Genes & development, 22 10:1276-312, May 2008. URL: https://doi.org/10.1101/gad.1653708, doi:10.1101/gad.1653708. This article has 3233 citations and is from a highest quality peer-reviewed journal.
(appelmann2010angiogenesisinhibitionin pages 11-14): Iris Appelmann, Rüediger Liersch, Torsten Kessler, Rolf M. Mesters, and Wolfgang E. Berdel. Angiogenesis inhibition in cancer therapy: platelet-derived growth factor (pdgf) and vascular endothelial growth factor (vegf) and their receptors: biological functions and role in malignancy. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, 180:51-81, Oct 2010. URL: https://doi.org/10.1007/978-3-540-78281-0_5, doi:10.1007/978-3-540-78281-0_5. This article has 114 citations.
(andrae2008roleofplateletderived pages 5-6): Johanna Andrae, Radiosa Gallini, and Christer Betsholtz. Role of platelet-derived growth factors in physiology and medicine. Genes & development, 22 10:1276-312, May 2008. URL: https://doi.org/10.1101/gad.1653708, doi:10.1101/gad.1653708. This article has 3233 citations and is from a highest quality peer-reviewed journal.
(appelmann2010angiogenesisinhibitionin pages 14-16): Iris Appelmann, Rüediger Liersch, Torsten Kessler, Rolf M. Mesters, and Wolfgang E. Berdel. Angiogenesis inhibition in cancer therapy: platelet-derived growth factor (pdgf) and vascular endothelial growth factor (vegf) and their receptors: biological functions and role in malignancy. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, 180:51-81, Oct 2010. URL: https://doi.org/10.1007/978-3-540-78281-0_5, doi:10.1007/978-3-540-78281-0_5. This article has 114 citations.
(forman2024pdgfrαsignalingregulates pages 1-2): Thomas E Forman, Marcin P Sajek, Eric D Larson, Neelanjan Mukherjee, and Katherine A Fantauzzo. Pdgfrα signaling regulates srsf3 transcript binding to affect pi3k signaling and endosomal trafficking. eLife, Dec 2024. URL: https://doi.org/10.7554/elife.98531, doi:10.7554/elife.98531. This article has 4 citations and is from a domain leading peer-reviewed journal.
(forman2024pdgfrαsignalingregulates pages 10-13): Thomas E Forman, Marcin P Sajek, Eric D Larson, Neelanjan Mukherjee, and Katherine A Fantauzzo. Pdgfrα signaling regulates srsf3 transcript binding to affect pi3k signaling and endosomal trafficking. eLife, Dec 2024. URL: https://doi.org/10.7554/elife.98531, doi:10.7554/elife.98531. This article has 4 citations and is from a domain leading peer-reviewed journal.
(yokota2024plateletderivedgrowthfactor pages 7-9): Kaito Yokota, Haruhiko Yamada, Hidetsugu Mori, Yuki Hattori, Masatoshi Omi, Yuichi Yamamoto, Keiko Toyama, and Hisanori Imai. Platelet-derived growth factor subunit a strengthens the neurovascular unit and inhibits retinal vascular regression under hyperoxic conditions. International Journal of Molecular Sciences, 25:12945, Dec 2024. URL: https://doi.org/10.3390/ijms252312945, doi:10.3390/ijms252312945. This article has 4 citations.
(yokota2024plateletderivedgrowthfactor pages 9-11): Kaito Yokota, Haruhiko Yamada, Hidetsugu Mori, Yuki Hattori, Masatoshi Omi, Yuichi Yamamoto, Keiko Toyama, and Hisanori Imai. Platelet-derived growth factor subunit a strengthens the neurovascular unit and inhibits retinal vascular regression under hyperoxic conditions. International Journal of Molecular Sciences, 25:12945, Dec 2024. URL: https://doi.org/10.3390/ijms252312945, doi:10.3390/ijms252312945. This article has 4 citations.
(OpenTargets Search: -PDGFA): Open Targets Query (-PDGFA, 8 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(andrae2008roleofplateletderived pages 25-26): Johanna Andrae, Radiosa Gallini, and Christer Betsholtz. Role of platelet-derived growth factors in physiology and medicine. Genes & development, 22 10:1276-312, May 2008. URL: https://doi.org/10.1101/gad.1653708, doi:10.1101/gad.1653708. This article has 3233 citations and is from a highest quality peer-reviewed journal.
(strell2024functionalandclinical media f86371c2): Carina Strell, Elisabet Rodríguez-Tomàs, and Arne Östman. Functional and clinical roles of stromal pdgf receptors in tumor biology. Cancer Metastasis Reviews, 43:1593-1609, Jul 2024. URL: https://doi.org/10.1007/s10555-024-10194-7, doi:10.1007/s10555-024-10194-7. This article has 26 citations.
(strell2024functionalandclinical media 0b99a6a7): Carina Strell, Elisabet Rodríguez-Tomàs, and Arne Östman. Functional and clinical roles of stromal pdgf receptors in tumor biology. Cancer Metastasis Reviews, 43:1593-1609, Jul 2024. URL: https://doi.org/10.1007/s10555-024-10194-7, doi:10.1007/s10555-024-10194-7. This article has 26 citations.
(yokota2024plateletderivedgrowthfactor pages 1-2): Kaito Yokota, Haruhiko Yamada, Hidetsugu Mori, Yuki Hattori, Masatoshi Omi, Yuichi Yamamoto, Keiko Toyama, and Hisanori Imai. Platelet-derived growth factor subunit a strengthens the neurovascular unit and inhibits retinal vascular regression under hyperoxic conditions. International Journal of Molecular Sciences, 25:12945, Dec 2024. URL: https://doi.org/10.3390/ijms252312945, doi:10.3390/ijms252312945. This article has 4 citations.
(jung2025rolesofpdgfpdgfr pages 1-2): Sung-Cherl Jung, Dawon Kang, and Eun-A Ko. Roles of pdgf/pdgfr signaling in various organs. The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 29:139-155, Oct 2025. URL: https://doi.org/10.4196/kjpp.24.309, doi:10.4196/kjpp.24.309. This article has 23 citations.

Citations

ma2024targetingpdgfpdgfrsignaling pages 1-2
andrae2008roleofplateletderived pages 1-2
strell2024functionalandclinical pages 1-3
basciani2010roleofplateletderived pages 3-5
andrae2008roleofplateletderived pages 25-26
yokota2024plateletderivedgrowthfactor pages 9-11
yokota2024plateletderivedgrowthfactor pages 7-9
appelmann2010angiogenesisinhibitionin pages 11-14
andrae2008roleofplateletderived pages 2-4
andrae2008roleofplateletderived pages 5-6
appelmann2010angiogenesisinhibitionin pages 14-16
yokota2024plateletderivedgrowthfactor pages 1-2
jung2025rolesofpdgfpdgfr pages 1-2
https://doi.org/10.1007/s10555-024-10194-7
https://doi.org/10.7554/elife.98531
https://doi.org/10.3390/ijms252312945
https://doi.org/10.3390/biom14111446
https://doi.org/10.1101/gad.1653708
https://doi.org/10.1210/er.2010-0004
https://doi.org/10.1007/978-3-540-78281-0_5
https://doi.org/10.1101/gad.1653708,
https://doi.org/10.1210/er.2010-0004,
https://doi.org/10.1007/s10555-024-10194-7,
https://doi.org/10.3390/biom14111446,
https://doi.org/10.1007/978-3-540-78281-0_5,
https://doi.org/10.7554/elife.98531,
https://doi.org/10.3390/ijms252312945,
https://doi.org/10.4196/kjpp.24.309,

📄 View Raw YAML

id: P04085
gene_symbol: PDGFA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'PDGFA encodes platelet-derived growth factor subunit A, a secreted PDGF/VEGF-family cystine-knot
  ligand that forms disulfide-linked PDGF-AA homodimers and PDGF-AB heterodimers. Its core function is
  extracellular/pericellular PDGF receptor ligand activity, primarily activating PDGFR-alpha signaling
  to drive local mesenchymal proliferation, migration, PI3K-Akt and MAPK/ERK signaling, angiogenic and
  wound-repair responses.'
existing_annotations:
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: &id001
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: 'PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**:
        it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate
        **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.'
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Across authoritative syntheses, PDGF ligands (including PDGF-AA) are
        emphasized as **local/paracrine factors** that regulate mesenchymal cell behaviors
        (proliferation, chemotaxis, matrix contraction) in development and tissue
        maintenance/repair.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of cell migration is a supported cellular response to PDGFA
      growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Angiogenesis is supported as an important PDGFA-associated tissue process.
    action: ACCEPT
    reason: PDGF-A/PDGFR signaling supports local mesenchymal and neurovascular behaviors relevant
      to angiogenesis and vascular stability.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Across authoritative syntheses, PDGF ligands (including PDGF-AA) are
        emphasized as **local/paracrine factors** that regulate mesenchymal cell behaviors
        (proliferation, chemotaxis, matrix contraction) in development and tissue
        maintenance/repair.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: In a 2024 oxygen-induced retinopathy (OIR) mouse model, retinal **PDGF-A
        overexpression** increased astrocyte-associated markers (e.g., GFAP, Pax2), increased
        **PDGFRα** expression in astrocyte-rich regions, increased vascular density, and reduced the
        area of vascular regression immediately after hyperoxic exposure—supporting a role for
        PDGF-A/PDGFRα signaling in astrocyte support and neurovascular stability under hyperoxic
        stress.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction is a supported downstream PDGFR signaling output.
    action: ACCEPT
    reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of
      receptor autophosphorylation.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing
        of transcripts involved in **PI3K signaling and endosomal trafficking**; Srsf3 activity in
        this context contributes to **retention of PDGFRα in early endosomes** and **amplifies
        PI3K-mediated Akt signaling**, linking receptor trafficking to signaling output.
- term:
    id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: platelet-derived growth factor receptor signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: &id002
    - &id004
      reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: 'PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**:
        it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate
        **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.'
    - &id005
      reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: A key specificity for PDGFA biology is that **PDGF-AA preferentially induces
        PDGFRα homodimers**, while PDGF-BB can engage broader receptor combinations; PDGF-DD is
        biased toward PDGFRβ-containing dimers.
    - &id006
      reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
- term:
    id: GO:0005161
    label: platelet-derived growth factor receptor binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular
      function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: extracellular space is consistent with secreted, extracellular, and pericellular PDGF-A
      ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: &id003
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Because PDGF-A is secreted and can be **pericellular ECM-bound** or
        **soluble** depending on splice isoform, its principal site of action is the **extracellular
        space** in the local tissue microenvironment, acting on **cell-surface PDGFRα/β** on
        neighboring responsive cells.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: A distinctive functional feature of PDGF-A is that **alternative splicing**
        generates isoforms with or without a **basic C-terminal “retention motif.”**
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of ERK1 and ERK2 cascade is a supported downstream PDGFR signaling
      output.
    action: ACCEPT
    reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of
      receptor autophosphorylation.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing
        of transcripts involved in **PI3K signaling and endosomal trafficking**; Srsf3 activity in
        this context contributes to **retention of PDGFRα in early endosomes** and **amplifies
        PI3K-mediated Akt signaling**, linking receptor trafficking to signaling output.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0008083
    label: growth factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: growth factor activity is a core PDGFA ligand molecular function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but is not
      the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: &id010
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-A (and PDGF-B) are synthesized as **disulfide-linked propeptide dimers**
        and require **intracellular N-terminal prodomain removal** by **furin or related proprotein
        convertases** during trafficking through the secretory pathway.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: A distinctive functional feature of PDGF-A is that **alternative splicing**
        generates isoforms with or without a **basic C-terminal “retention motif.”**
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: receptor ligand activity is a core PDGFA ligand molecular function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:0051781
    label: positive regulation of cell division
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: positive regulation of cell division is a supported cellular response to PDGFA
      growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25241761
  review:
    summary: Protein binding is supported only as a generic description of more specific PDGF
      receptor and dimer interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative molecular functions are PDGF receptor binding/receptor ligand activity
      and PDGF dimerization, not generic protein binding.
    proposed_replacement_terms: &id007
    - id: GO:0005161
      label: platelet-derived growth factor receptor binding
    - id: GO:0048018
      label: receptor ligand activity
    supported_by:
    - *id004
    - *id005
    - *id006
    - &id008
      reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: The UniProt accession **P04085** corresponds to human **PDGFA** encoding
        **platelet-derived growth factor subunit A (PDGF-A chain)**, a secreted **PDGF/VEGF-family
        cystine-knot growth factor** produced as a **precursor** and functioning as a
        **disulfide-linked dimeric ligand** (commonly **PDGF-AA**, also **PDGF-AB**).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:7679113
  review:
    summary: Protein binding is supported only as a generic description of more specific PDGF
      receptor and dimer interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative molecular functions are PDGF receptor binding/receptor ligand activity
      and PDGF dimerization, not generic protein binding.
    proposed_replacement_terms: *id007
    supported_by:
    - *id004
    - *id005
    - *id006
    - *id008
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: extracellular space is consistent with secreted, extracellular, and pericellular PDGF-A
      ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005902
    label: microvillus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Microvillus localization is not supported by the PDGFA evidence and is likely
      over-specific for this secreted/pericellular ligand.
    action: MARK_AS_OVER_ANNOTATED
    reason: The Falcon synthesis supports extracellular, pericellular, and secretory-pathway
      contexts, but does not provide evidence that microvillus is an informative PDGFA localization.
    proposed_replacement_terms:
    - id: GO:0005615
      label: extracellular space
    - id: GO:0005576
      label: extracellular region
    supported_by:
    - &id011
      reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Because PDGF-A is secreted and can be **pericellular ECM-bound** or
        **soluble** depending on splice isoform, its principal site of action is the **extracellular
        space** in the local tissue microenvironment, acting on **cell-surface PDGFRα/β** on
        neighboring responsive cells.
- term:
    id: GO:0048565
    label: digestive tract development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: digestive tract development is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: &id009
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Across authoritative syntheses, PDGF ligands (including PDGF-AA) are
        emphasized as **local/paracrine factors** that regulate mesenchymal cell behaviors
        (proliferation, chemotaxis, matrix contraction) in development and tissue
        maintenance/repair.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: 'PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**:
        it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate
        **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.'
- term:
    id: GO:1990401
    label: embryonic lung development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: embryonic lung development is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0035790
    label: platelet-derived growth factor receptor-alpha signaling pathway
  evidence_type: NAS
  original_reference_id: PMID:11297552
  review:
    summary: platelet-derived growth factor receptor-alpha signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: *id002
- term:
    id: GO:0038083
    label: peptidyl-tyrosine autophosphorylation
  evidence_type: NAS
  original_reference_id: PMID:11297552
  review:
    summary: Peptidyl-tyrosine autophosphorylation is receptor biology, not a process carried out by
      PDGFA.
    action: REMOVE
    reason: PDGF-A ligand binding induces PDGFR autophosphorylation, but PDGFA itself is not a
      kinase and does not catalyze or autophosphorylate proteins.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: 'PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**:
        it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate
        **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.'
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
- term:
    id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  evidence_type: NAS
  original_reference_id: PMID:7679113
  review:
    summary: platelet-derived growth factor receptor signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: *id002
- term:
    id: GO:0035790
    label: platelet-derived growth factor receptor-alpha signaling pathway
  evidence_type: NAS
  original_reference_id: PMID:7679113
  review:
    summary: platelet-derived growth factor receptor-alpha signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: *id002
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:10806482
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:2439522
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186785
  review:
    summary: Golgi lumen is plausible for PDGF-A biosynthesis, storage, or isoform retention but is
      not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8865276
  review:
    summary: Golgi lumen is plausible for PDGF-A biosynthesis, storage, or isoform retention but is
      not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0005161
    label: platelet-derived growth factor receptor binding
  evidence_type: IDA
  original_reference_id: PMID:2439522
  review:
    summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular
      function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:1990401
    label: embryonic lung development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: embryonic lung development is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0008083
    label: growth factor activity
  evidence_type: IDA
  original_reference_id: PMID:12070119
  review:
    summary: growth factor activity is a core PDGFA ligand molecular function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:2538439
  review:
    summary: cell surface is consistent with secreted, extracellular, and pericellular PDGF-A ligand
      action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186785
  review:
    summary: Golgi membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but
      is not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382053
  review:
    summary: Golgi membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but
      is not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1524182
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1524186
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186765
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186773
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186778
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186780
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186785
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186800
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186819
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186826
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186834
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2316434
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2400009
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380780
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380782
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382052
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382054
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382055
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382056
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382058
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389083
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-481007
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672965
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9674093
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382053
  review:
    summary: endoplasmic reticulum lumen is plausible for PDGF-A biosynthesis, storage, or isoform
      retention but is not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0031093
    label: platelet alpha granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-481007
  review:
    summary: platelet alpha granule lumen is plausible for PDGF-A biosynthesis, storage, or isoform
      retention but is not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8865276
  review:
    summary: Golgi membrane is plausible for PDGF-A biosynthesis, storage, or isoform retention but
      is not the principal site of action.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A is synthesized and processed through the secretory pathway, but its core function
      is extracellular receptor-ligand signaling.
    supported_by: *id010
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2396337
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389086
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8864036
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8865276
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9796072
  review:
    summary: extracellular region is consistent with secreted, extracellular, and pericellular
      PDGF-A ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0035793
    label: positive regulation of metanephric mesenchymal cell migration by platelet-derived growth
      factor receptor-beta signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:19019919
  review:
    summary: positive regulation of metanephric mesenchymal cell migration by platelet-derived
      growth factor receptor-beta signaling pathway is plausible downstream PDGFA biology but
      secondary to the core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Angiogenesis is supported as an important PDGFA-associated tissue process.
    action: ACCEPT
    reason: PDGF-A/PDGFR signaling supports local mesenchymal and neurovascular behaviors relevant
      to angiogenesis and vascular stability.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Across authoritative syntheses, PDGF ligands (including PDGF-AA) are
        emphasized as **local/paracrine factors** that regulate mesenchymal cell behaviors
        (proliferation, chemotaxis, matrix contraction) in development and tissue
        maintenance/repair.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: In a 2024 oxygen-induced retinopathy (OIR) mouse model, retinal **PDGF-A
        overexpression** increased astrocyte-associated markers (e.g., GFAP, Pax2), increased
        **PDGFRα** expression in astrocyte-rich regions, increased vascular density, and reduced the
        area of vascular regression immediately after hyperoxic exposure—supporting a role for
        PDGF-A/PDGFRα signaling in astrocyte support and neurovascular stability under hyperoxic
        stress.
- term:
    id: GO:0001942
    label: hair follicle development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: hair follicle development is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0002053
    label: positive regulation of mesenchymal cell proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of mesenchymal cell proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0005902
    label: microvillus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Microvillus localization is not supported by the PDGFA evidence and is likely
      over-specific for this secreted/pericellular ligand.
    action: MARK_AS_OVER_ANNOTATED
    reason: The Falcon synthesis supports extracellular, pericellular, and secretory-pathway
      contexts, but does not provide evidence that microvillus is an informative PDGFA localization.
    proposed_replacement_terms:
    - id: GO:0005615
      label: extracellular space
    - id: GO:0005576
      label: extracellular region
    supported_by:
    - *id011
- term:
    id: GO:0009887
    label: animal organ morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: animal organ morphogenesis is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0030031
    label: cell projection assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cell projection assembly is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0030036
    label: actin cytoskeleton organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: actin cytoskeleton organization is plausible downstream PDGFA biology but secondary to
      the core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0043588
    label: skin development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: skin development is plausible downstream PDGFA biology but secondary to the core
      receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0048286
    label: lung alveolus development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: lung alveolus development is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0060683
    label: regulation of branching involved in salivary gland morphogenesis by
      epithelial-mesenchymal signaling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: regulation of branching involved in salivary gland morphogenesis by
      epithelial-mesenchymal signaling is plausible downstream PDGFA biology but secondary to the
      core receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IDA
  original_reference_id: PMID:11788434
  review:
    summary: positive regulation of cell migration is a supported cellular response to PDGFA
      growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IMP
  original_reference_id: PMID:11788434
  review:
    summary: positive regulation of MAPK cascade is a supported downstream PDGFR signaling output.
    action: ACCEPT
    reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of
      receptor autophosphorylation.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing
        of transcripts involved in **PI3K signaling and endosomal trafficking**; Srsf3 activity in
        this context contributes to **retention of PDGFRα in early endosomes** and **amplifies
        PI3K-mediated Akt signaling**, linking receptor trafficking to signaling output.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IDA
  original_reference_id: PMID:11788434
  review:
    summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction is a supported downstream PDGFR signaling output.
    action: ACCEPT
    reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of
      receptor autophosphorylation.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing
        of transcripts involved in **PI3K signaling and endosomal trafficking**; Srsf3 activity in
        this context contributes to **retention of PDGFRα in early endosomes** and **amplifies
        PI3K-mediated Akt signaling**, linking receptor trafficking to signaling output.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IDA
  original_reference_id: PMID:19019919
  review:
    summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction is a supported downstream PDGFR signaling output.
    action: ACCEPT
    reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of
      receptor autophosphorylation.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing
        of transcripts involved in **PI3K signaling and endosomal trafficking**; Srsf3 activity in
        this context contributes to **retention of PDGFRα in early endosomes** and **amplifies
        PI3K-mediated Akt signaling**, linking receptor trafficking to signaling output.
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IDA
  original_reference_id: PMID:11788434
  review:
    summary: positive regulation of ERK1 and ERK2 cascade is a supported downstream PDGFR signaling
      output.
    action: ACCEPT
    reason: PDGFA/PDGFR signaling activates canonical PI3K-Akt and MAPK/ERK pathways downstream of
      receptor autophosphorylation.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs signal through two receptor tyrosine kinases, **PDGFRα** and
        **PDGFRβ**. Ligand binding induces receptor **dimerization** and **autophosphorylation** of
        intracellular tyrosines, generating docking sites for downstream signaling proteins.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGF-AA stimulation changes Srsf3 binding patterns and alternative splicing
        of transcripts involved in **PI3K signaling and endosomal trafficking**; Srsf3 activity in
        this context contributes to **retention of PDGFRα in early endosomes** and **amplifies
        PI3K-mediated Akt signaling**, linking receptor trafficking to signaling output.
- term:
    id: GO:0072124
    label: regulation of glomerular mesangial cell proliferation
  evidence_type: IDA
  original_reference_id: PMID:11788434
  negated: true
  review:
    summary: 'Negated annotation: the cited metanephric mesenchymal-cell study found that PDGF-A/PDGF-AA
      did not drive the mesangial-cell proliferative response measured through DNA synthesis.'
    action: ACCEPT
    reason: This NOT annotation should be retained because the cited experiment supports absence of
      this PDGFA proliferative response in the tested metanephric mesenchyme context.
    supported_by:
    - &id012
      reference_id: PMID:11788434
      supporting_text: PDGF AA caused modest cell migration but had no effect on DNA synthesis,
        unlike PDGF BB, which potently stimulated migration and DNA synthesis.
- term:
    id: GO:2000278
    label: regulation of DNA biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:11788434
  negated: true
  review:
    summary: 'Negated annotation: this row should not be read as a positive DNA-synthesis function;
      PDGF-A/PDGF-AA lacked the cited metanephric mesenchyme response, with the clearest DNA-synthesis
      support coming from the paired PMID:11788434 evidence.'
    action: ACCEPT
    reason: The annotation is a NOT assertion and should be retained, but the PMID:19019919 abstract
      supports absence of a PDGF-AA response in this context rather than a positive non-core function.
    supported_by:
    - *id012
- term:
    id: GO:2000278
    label: regulation of DNA biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:19019919
  negated: true
  review:
    summary: 'Negated annotation: the cited metanephric mesenchyme evidence indicates that PDGF-A/PDGF-AA
      did not stimulate the DNA-synthesis response in the tested context.'
    action: ACCEPT
    reason: The annotation is a NOT assertion and should be retained as evidence that PDGFA lacks
      this DNA-biosynthetic/mitogenic effect in those experiments, rather than described as a
      positive non-core function.
    supported_by:
    - reference_id: PMID:19019919
      supporting_text: PDGF BB stimulated cell migration in +/+ cells, whereas PDGF AA did not.
    - *id012
- term:
    id: GO:0005518
    label: collagen binding
  evidence_type: IDA
  original_reference_id: PMID:8900172
  review:
    summary: Collagen/ECM binding is consistent with extracellular matrix-associated PDGF-A
      localization but is not the core ligand activity.
    action: KEEP_AS_NON_CORE
    reason: PDGF-A spatial range is shaped by extracellular/pericellular retention; receptor binding
      remains the core molecular function.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: A distinctive functional feature of PDGF-A is that **alternative splicing**
        generates isoforms with or without a **basic C-terminal “retention motif.”**
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Because PDGF-A is secreted and can be **pericellular ECM-bound** or
        **soluble** depending on splice isoform, its principal site of action is the **extracellular
        space** in the local tissue microenvironment, acting on **cell-surface PDGFRα/β** on
        neighboring responsive cells.
- term:
    id: GO:0014910
    label: regulation of smooth muscle cell migration
  evidence_type: IDA
  original_reference_id: PMID:9409235
  review:
    summary: regulation of smooth muscle cell migration is a supported cellular response to PDGFA
      growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0050919
    label: negative chemotaxis
  evidence_type: IDA
  original_reference_id: PMID:9409235
  review:
    summary: negative chemotaxis is plausible downstream PDGFA biology but secondary to the core
      receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0001775
    label: cell activation
  evidence_type: TAS
  original_reference_id: PMID:10508235
  review:
    summary: cell activation is plausible downstream PDGFA biology but secondary to the core
      receptor-ligand signaling function.
    action: KEEP_AS_NON_CORE
    reason: These developmental, cytoskeletal, migration, or cell-state outputs reflect
      context-specific consequences of PDGF-A/PDGFR signaling.
    supported_by: *id009
- term:
    id: GO:0005161
    label: platelet-derived growth factor receptor binding
  evidence_type: IPI
  original_reference_id: PMID:2536956
  review:
    summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular
      function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:17470632
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IDA
  original_reference_id: PMID:17470632
  review:
    summary: positive regulation of cell migration is a supported cellular response to PDGFA
      growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: TAS
  original_reference_id: PMID:10508235
  review:
    summary: regulation of actin cytoskeleton organization is secondary to PDGFA secreted
      receptor-ligand signaling.
    action: KEEP_AS_NON_CORE
    reason: The core PDGFA function is extracellular PDGF receptor ligand activity.
    supported_by: *id002
- term:
    id: GO:0042060
    label: wound healing
  evidence_type: TAS
  original_reference_id: PMID:10508235
  review:
    summary: wound healing is a supported tissue-level PDGF pathway role.
    action: ACCEPT
    reason: PDGF signaling has well-established relevance to wound repair and local mesenchymal
      responses.
    supported_by: &id013
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: A widely cited clinical application of the PDGF system is topical PDGF-based
        therapy for chronic wounds; a large clinical study (>900 patients) is summarized as showing
        topical PDGF improved healing of chronic full-thickness diabetic foot ulcers.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Across authoritative syntheses, PDGF ligands (including PDGF-AA) are
        emphasized as **local/paracrine factors** that regulate mesenchymal cell behaviors
        (proliferation, chemotaxis, matrix contraction) in development and tissue
        maintenance/repair.
- term:
    id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:2536956
  review:
    summary: platelet-derived growth factor receptor signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: *id002
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: IDA
  original_reference_id: PMID:10806482
  review:
    summary: positive regulation of fibroblast proliferation is a supported cellular response to
      PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0005161
    label: platelet-derived growth factor receptor binding
  evidence_type: IDA
  original_reference_id: PMID:2836953
  review:
    summary: platelet-derived growth factor receptor binding is a core PDGFA ligand molecular
      function.
    action: ACCEPT
    reason: PDGFA encodes a secreted PDGF-A ligand that binds and activates PDGF receptor complexes,
      especially PDGFRα.
    supported_by: *id002
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:3754619
  review:
    summary: extracellular space is consistent with secreted, extracellular, and pericellular PDGF-A
      ligand action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:2836953
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:7073684
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0009611
    label: response to wounding
  evidence_type: IDA
  original_reference_id: PMID:2538439
  review:
    summary: response to wounding is a supported tissue-level PDGF pathway role.
    action: ACCEPT
    reason: PDGF signaling has well-established relevance to wound repair and local mesenchymal
      responses.
    supported_by: *id013
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:2836953
  review:
    summary: cell surface is consistent with secreted, extracellular, and pericellular PDGF-A ligand
      action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:291037
  review:
    summary: cell surface is consistent with secreted, extracellular, and pericellular PDGF-A ligand
      action.
    action: ACCEPT
    reason: PDGFA acts in the extracellular/pericellular tissue microenvironment and on cell-surface
      receptor-bearing cells.
    supported_by: *id003
- term:
    id: GO:0010512
    label: negative regulation of phosphatidylinositol biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:2538439
  review:
    summary: negative regulation of phosphatidylinositol biosynthetic process is supported by older
      platelet-response evidence but is not a core PDGFA function.
    action: KEEP_AS_NON_CORE
    reason: This platelet-feedback biology is secondary to the main secreted growth-factor ligand
      role.
    supported_by:
    - &id014
      reference_id: PMID:2538439
      supporting_text: Platelet-derived growth factor (PDGF) is known to inhibit collagen-induced
        platelet aggregation.
    - &id015
      reference_id: PMID:2538439
      supporting_text: These results suggest that (i) a specific PDGF receptor can be induced by
        collagen, and (ii) PDGF can effect the early events of collagen-induced platelet activation
        by inhibiting PIP2 resynthesis and P43 and P20 phosphorylation.
- term:
    id: GO:0010544
    label: negative regulation of platelet activation
  evidence_type: IDA
  original_reference_id: PMID:2538439
  review:
    summary: negative regulation of platelet activation is supported by older platelet-response
      evidence but is not a core PDGFA function.
    action: KEEP_AS_NON_CORE
    reason: This platelet-feedback biology is secondary to the main secreted growth-factor ligand
      role.
    supported_by:
    - *id014
    - *id015
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:2836953
  review:
    summary: protein homodimerization activity is consistent with PDGF-A dimeric ligand assembly.
    action: ACCEPT
    reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are
      the signaling ligand forms.
    supported_by: &id016
    - *id008
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: PDGFs are secreted growth factors that function as **disulfide-linked
        dimers**.
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: '**PDGFA** contributes the **A-chain**, which most commonly forms the **PDGF-AA
        homodimer**; **PDGF-AB** has been detected in human platelets.'
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:3754619
  review:
    summary: protein homodimerization activity is consistent with PDGF-A dimeric ligand assembly.
    action: ACCEPT
    reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are
      the signaling ligand forms.
    supported_by: *id016
- term:
    id: GO:0046982
    label: protein heterodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:7073684
  review:
    summary: protein heterodimerization activity is consistent with PDGF-A dimeric ligand assembly.
    action: ACCEPT
    reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are
      the signaling ligand forms.
    supported_by: *id016
- term:
    id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:2439522
  review:
    summary: platelet-derived growth factor receptor signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: *id002
- term:
    id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:2836953
  review:
    summary: platelet-derived growth factor receptor signaling pathway is the core
      receptor-signaling pathway for PDGFA.
    action: ACCEPT
    reason: PDGF-A acts as an extracellular ligand for PDGFR signaling, with PDGFRα-biased signaling
      most central.
    supported_by: *id002
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: IDA
  original_reference_id: PMID:2439522
  review:
    summary: positive regulation of fibroblast proliferation is a supported cellular response to
      PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0048407
    label: platelet-derived growth factor binding
  evidence_type: IPI
  original_reference_id: PMID:7073684
  review:
    summary: platelet-derived growth factor binding is consistent with PDGF-A dimeric ligand
      assembly.
    action: ACCEPT
    reason: PDGFA contributes the A-chain to PDGF-AA homodimers and PDGF-AB heterodimers, which are
      the signaling ligand forms.
    supported_by: *id016
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:16462734
  review:
    summary: positive regulation of cell population proliferation is a supported cellular response
      to PDGFA growth-factor signaling.
    action: ACCEPT
    reason: Proliferation, migration, chemotaxis, and matrix-remodeling behaviors are central
      PDGF-A/PDGFR biological outputs.
    supported_by: *id001
- term:
    id: GO:0007267
    label: cell-cell signaling
  evidence_type: TAS
  original_reference_id: PMID:2842868
  review:
    summary: Cell-cell signaling captures the paracrine signaling nature of PDGFA.
    action: ACCEPT
    reason: PDGF-A is a local extracellular/paracrine ligand acting between source and
      PDGFR-expressing target cells.
    supported_by:
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: 'PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**:
        it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate
        **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.'
    - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
      supporting_text: Because PDGF-A is secreted and can be **pericellular ECM-bound** or
        **soluble** depending on splice isoform, its principal site of action is the **extracellular
        space** in the local tissue microenvironment, acting on **cell-surface PDGFRα/β** on
        neighboring responsive cells.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by
    curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
    mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
    Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10508235
  title: Mechanism of action and in vivo role of platelet-derived growth factor.
  findings: []
- id: PMID:10806482
  title: PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.
  findings: []
- id: PMID:11297552
  title: Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha
    and beta receptor.
  findings: []
- id: PMID:11788434
  title: Effect of platelet-derived growth factor isoforms in rat metanephric mesenchymal cells.
  findings: []
- id: PMID:12070119
  title: Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth
    factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in
    vascular smooth muscle cell.
  findings: []
- id: PMID:16462734
  title: VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain.
  findings: []
- id: PMID:17470632
  title: Vascular endothelial growth factor can signal through platelet-derived growth factor
    receptors.
  findings: []
- id: PMID:19019919
  title: PDGF receptor-{beta} modulates metanephric mesenchyme chemotaxis induced by PDGF AA.
  findings: []
- id: PMID:2439522
  title: PDGF induces c-myc mRNA expression in MG-63 human osteosarcoma cells but does not stimulate
    cell replication.
  findings: []
- id: PMID:25241761
  title: Using an in situ proximity ligation assay to systematically profile endogenous
    protein-protein interactions in a pathway network.
  findings: []
- id: PMID:2536956
  title: Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes.
  findings: []
- id: PMID:2538439
  title: Collagen-induced binding to human platelets of platelet-derived growth factor leading to
    inhibition of P43 and P20 phosphorylation.
  findings: []
- id: PMID:2836953
  title: A common PDGF receptor is activated by homodimeric A and B forms of PDGF.
  findings: []
- id: PMID:2842868
  title: Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B
    chains.
  findings: []
- id: PMID:291037
  title: 'Platelet-derived growth factor: purification and partial characterization.'
  findings: []
- id: PMID:3754619
  title: cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain
    and its expression in tumour cell lines.
  findings: []
- id: PMID:7073684
  title: 'Platelet-derived growth factor: identification of constituent polypeptide chains.'
  findings: []
- id: PMID:7679113
  title: Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta
    PDGF receptor.
  findings: []
- id: PMID:8900172
  title: Type I, II, III, IV, V, and VI collagens serve as extracellular ligands for the isoforms of
    platelet-derived growth factor (AA, BB, and AB).
  findings: []
- id: PMID:9409235
  title: Platelet-derived growth factor beta-receptors can both promote and inhibit chemotaxis in
    human vascular smooth muscle cells.
  findings: []
- id: Reactome:R-HSA-1524182
  title: Activated PLC gamma dissociates from the PDGF receptor
  findings: []
- id: Reactome:R-HSA-1524186
  title: Phosphorylation of PLCgamma by PDGFR
  findings: []
- id: Reactome:R-HSA-186765
  title: PLC-gamma binds to the active receptor
  findings: []
- id: Reactome:R-HSA-186773
  title: PDGF dimer binds two receptors simultaneously
  findings: []
- id: Reactome:R-HSA-186778
  title: SHP2 binds to the active receptor
  findings: []
- id: Reactome:R-HSA-186780
  title: PI3-kinase binds to the active receptor
  findings: []
- id: Reactome:R-HSA-186785
  title: PDGF-AA clevage by Furin
  findings: []
- id: Reactome:R-HSA-186800
  title: PI3K catalyses the phosphorylation of PIP2 to PIP3
  findings: []
- id: Reactome:R-HSA-186819
  title: SH2 domain of Src binds to the active receptor
  findings: []
- id: Reactome:R-HSA-186826
  title: GRB2:SOS1 complex binds to the active receptor
  findings: []
- id: Reactome:R-HSA-186834
  title: SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)
  findings: []
- id: Reactome:R-HSA-2316434
  title: PI3K phosphorylates PIP2 to PIP3
  findings: []
- id: Reactome:R-HSA-2396337
  title: HSPG2 binds FGF2(10-155), Fibronectn matrix, Transthyretin tetramer, PDGFA homodimer, PDGFB
    homodimer
  findings: []
- id: Reactome:R-HSA-2400009
  title: PI3K inhibitors block PI3K catalytic activity
  findings: []
- id: Reactome:R-HSA-380780
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-380782
  title: STAT binds to the active receptor
  findings: []
- id: Reactome:R-HSA-382052
  title: p130Cas and C3G bind PDGFR bound Crk
  findings: []
- id: Reactome:R-HSA-382053
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-382054
  title: PDGF binds to extracellular matrix proteins
  findings: []
- id: Reactome:R-HSA-382055
  title: Grb7 binds to the active PDGF receptor
  findings: []
- id: Reactome:R-HSA-382056
  title: Crk binds to the active PDGF receptor
  findings: []
- id: Reactome:R-HSA-382058
  title: Nck binds to the active PDGF receptor
  findings: []
- id: Reactome:R-HSA-389083
  title: Autophosphorylation of PDGF alpha receptors
  findings: []
- id: Reactome:R-HSA-389086
  title: Autophosphorylation of PDGF alpha/beta receptors
  findings: []
- id: Reactome:R-HSA-481007
  title: Exocytosis of platelet alpha granule contents
  findings: []
- id: Reactome:R-HSA-5672965
  title: RAS GEFs promote RAS nucleotide exchange
  findings: []
- id: Reactome:R-HSA-8864036
  title: PTPN12 dephosphorylates PDGFRB at Y1021
  findings: []
- id: Reactome:R-HSA-8865276
  title: PDGF-AB clevage by Furin
  findings: []
- id: Reactome:R-HSA-9674093
  title: PDGFRs bind type I TKI
  findings: []
- id: Reactome:R-HSA-9796072
  title: NFE2L2 dependent PDGFA expression
  findings: []
- id: file:human/PDGFA/PDGFA-deep-research-falcon.md
  title: Falcon deep research synthesis for PDGFA
  findings: []
core_functions:
- description: Secreted dimeric PDGF-A receptor ligand activity, mainly as PDGF-AA, activating
    PDGFR-alpha-biased receptor signaling in the extracellular/pericellular microenvironment.
  molecular_function:
    id: GO:0005161
    label: platelet-derived growth factor receptor binding
  directly_involved_in:
  - id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  - id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  - id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  - id: GO:0008284
    label: positive regulation of cell population proliferation
  - id: GO:0030335
    label: positive regulation of cell migration
  locations:
  - id: GO:0005576
    label: extracellular region
  - id: GO:0009986
    label: cell surface
  supported_by:
  - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
    supporting_text: The UniProt accession **P04085** corresponds to human **PDGFA** encoding
      **platelet-derived growth factor subunit A (PDGF-A chain)**, a secreted **PDGF/VEGF-family
      cystine-knot growth factor** produced as a **precursor** and functioning as a
      **disulfide-linked dimeric ligand** (commonly **PDGF-AA**, also **PDGF-AB**).
  - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
    supporting_text: '**PDGFA** contributes the **A-chain**, which most commonly forms the **PDGF-AA homodimer**;
      **PDGF-AB** has been detected in human platelets.'
  - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
    supporting_text: A key specificity for PDGFA biology is that **PDGF-AA preferentially induces
      PDGFRα homodimers**, while PDGF-BB can engage broader receptor combinations; PDGF-DD is biased
      toward PDGFRβ-containing dimers.
  - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
    supporting_text: 'PDGF-A’s “primary function” in functional-annotation terms is **paracrine signaling**:
      it acts as an extracellular ligand that activates **PDGFRα (primarily)** on target cells to regulate
      **proliferation, survival, chemotaxis/migration, and matrix remodeling behaviors**.'
  - reference_id: file:human/PDGFA/PDGFA-deep-research-falcon.md
    supporting_text: Because PDGF-A is secreted and can be **pericellular ECM-bound** or **soluble**
      depending on splice isoform, its principal site of action is the **extracellular space** in
      the local tissue microenvironment, acting on **cell-surface PDGFRα/β** on neighboring
      responsive cells.
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []

PDGFA

Gene Description

Existing Annotations Review

Core Functions

Secreted dimeric PDGF-A receptor ligand activity, mainly as PDGF-AA, activating PDGFR-alpha-biased receptor signaling in the extracellular/pericellular microenvironment.

References

Deep Research

Falcon

Research report: Human PDGFA (UniProt P04085) – functional annotation

0) Target verification (gene/protein identity)

1) Key concepts, definitions, and current understanding

1.1 PDGF ligands and dimerization nomenclature

1.2 Receptor system and ligand–receptor specificity

1.3 PDGFA is a signaling ligand (not an enzyme)

2) Molecular biology of PDGFA protein: synthesis, processing, and localization

2.1 Biosynthesis and proteolytic maturation

2.2 Alternative splicing and extracellular matrix (ECM)/pericellular retention

2.3 Where PDGFA acts (cellular/extracellular localization)

3) Signaling pathways downstream of PDGF-AA/PDGFRα

3.1 Canonical signaling modules

3.2 Recent mechanistic advance (2024): coupling to alternative splicing and endosomal signaling

4) Physiological roles and biological processes (focused functional annotation)

4.1 Core biological role: local mesenchymal regulation

4.2 Neurovascular unit / retina (2024)

4.3 Developmental craniofacial context (2024)

5) Disease associations and clinical relevance

5.1 Fibrosis and stromal remodeling

5.2 Tumor microenvironment (2024 review perspective)

5.3 Structured database evidence (Open Targets)

6) Current applications and real-world implementations

6.1 Therapeutic strategies targeting the PDGF/PDGFR axis

6.2 Regenerative medicine and wound healing (historical but still clinically informative)

6.3 Emerging/experimental implementation: retinal vascular stabilization

7) Expert interpretation and synthesis (authoritative perspectives)

7.1 Spatial control is a defining functional principle for PDGFA

7.2 Signaling output depends on receptor trafficking and post-receptor regulation

8) Visual evidence: ligand–receptor specificity and signaling overview

Summary table

Key sources (publication date, URL)

Citations

📄 View Raw YAML