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.
| 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 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 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. |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)