Kdr (VEGFR-2, Flk-1) is a single-pass type I transmembrane receptor tyrosine kinase of the CSF-1/PDGF receptor subfamily, expressed mainly on vascular endothelial cells and also on endothelial and hematopoietic progenitors and some neurons. Its seven extracellular Ig-like domains bind VEGFA, VEGFC and VEGFD (via domains 2-3); ligand binding induces receptor dimerization and trans-autophosphorylation of the split intracellular kinase domain. The phosphotyrosines recruit PLCG1 (a direct substrate), PI3K, SHB, NCK1 and other adaptors, activating PKC/Ca2+, ERK1/2, PI3K-AKT, FAK and eNOS/NO outputs. VEGFR-2 signalling drives endothelial proliferation, survival, migration and tube formation and is essential for vasculogenesis, angiogenesis and embryonic hematopoiesis; it also mediates VEGF-induced vasodilation and vascular permeability. In rat, Kdr mediates VEGF-induced hypotension, ocular neovascularization and neurotrophic effects of VEGF on neurons (Ca2+ signalling, neurite outgrowth, hypoxic neuroprotection, hippocampal neurogenesis). Signalling is tuned by endosomal trafficking, heterodimerization with FLT1/FLT4, co-receptors such as neuropilins, and a short truncated isoform that retains ligand binding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: Kdr is the principal VEGF receptor driving angiogenesis. Reason: Core process; the IBA family node is sound and rat inhibitor/antibody studies agree (PMID:15951738, PMID:25942475). Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis PMID:15951738 Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization |
| GO:0001541 ovarian follicle development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ovarian follicle development (mouse IMP PMID:17050862, acts upstream), reflecting VEGF-driven follicular angiogenesis. Reason: Developmental context; non-core. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0001569 branching involved in blood vessel morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Branching blood vessel morphogenesis (human donor, acts upstream). Reason: Part of angiogenic sprouting; non-core restatement of angiogenesis. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0001570 vasculogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr (Flk-1) is required for embryonic vasculogenesis (mouse Flk1-null embryos lack blood islands and vessels). Reason: Core developmental role of the receptor, transferred from mouse orthologs. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0001570 vasculogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr (Flk-1) is required for embryonic vasculogenesis (mouse Flk1-null embryos lack blood islands and vessels). Reason: Core developmental role of the receptor, transferred from mouse orthologs. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0001570 vasculogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr (Flk-1) is required for embryonic vasculogenesis (mouse Flk1-null embryos lack blood islands and vessels). Reason: Core developmental role of the receptor, transferred from mouse orthologs. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0001666 response to hypoxia | IMP PMID:15780476 Reduction of a vascular endothelial growth factor receptor, ... | KEEP AS NON CORE | Summary: Flk-1 knock-down in rat spinal cord causes motor neuron loss only under hypoxia, through loss of Akt/ERK activation. Reason: Neuroprotective context of VEGF-Kdr signalling; non-core. Supporting Evidence: PMID:15780476 These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways PMID:15780476 In contrast, the reduction of Flk-1 expression alone did not induce motor neuron loss |
| GO:0001934 positive regulation of protein phosphorylation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Kdr promotes phosphorylation of downstream signalling proteins (FYN, NCK1, NOS3, PIK3R1, FAK, SRC). Reason: True; many of these are indirect via recruited kinases. Non-core. Supporting Evidence: UniProtKB:O08775 Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC |
| GO:0001936 regulation of endothelial cell proliferation | IEA GO_REF:0000117 | MODIFY | Summary: Regulation of endothelial cell proliferation (ARBA). Reason: The direction is known: Kdr signalling promotes endothelial proliferation (GO:0001938). Proposed replacements: positive regulation of endothelial cell proliferation Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:12052848 The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF |
| GO:0001938 positive regulation of endothelial cell proliferation | IMP PMID:17360578 VEGF is an essential mediator of the neurogenic and behavior... | ACCEPT | Summary: IMP from a rat antidepressant study showing Flk-1 signalling is required for antidepressant-induced cell proliferation. Reason: The abstract describes hippocampal progenitor proliferation; the endothelial readout must be in the full text, which the curator read. The function is well established for Kdr, so it is accepted. Supporting Evidence: PMID:17360578 We find that VEGF signaling through the Flk-1 receptor is required for antidepressant-induced cell proliferation UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr signalling promotes endothelial cell proliferation. Reason: Core cellular outcome of VEGF-Kdr signalling. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:12052848 The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF |
| GO:0001938 positive regulation of endothelial cell proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr signalling promotes endothelial cell proliferation. Reason: Core cellular outcome of VEGF-Kdr signalling. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:12052848 The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF |
| GO:0001945 lymph vessel development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lymph vessel development (mouse, acts upstream). Reason: VEGFR2 contributes with VEGFR3 to lymphatic growth; non-core. Supporting Evidence: UniProtKB:O08775 Modulates FLT1 and FLT4 signaling by forming heterodimers |
| GO:0002053 positive regulation of mesenchymal cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of mesenchymal cell proliferation from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0003085 negative regulation of systemic arterial blood pressure | IGI PMID:12052848 KDR (VEGF receptor 2) is the major mediator for the hypotens... | KEEP AS NON CORE | Summary: KDR is the predominant receptor for VEGF-induced hypotension in conscious rats. Reason: Physiological systemic consequence of endothelial VEGF signalling (NO-mediated); non-core. Supporting Evidence: PMID:12052848 KDR is the predominant receptor mediating this effect |
| GO:0003157 endocardium development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Endocardium development (mouse). Reason: Developmental context; non-core. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0003158 endothelium development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Endothelium development (mouse genetics and ARBA). Reason: True developmental context of Kdr; non-core. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0003158 endothelium development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Endothelium development (mouse genetics and ARBA). Reason: True developmental context of Kdr; non-core. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0003158 endothelium development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endothelium development (mouse genetics and ARBA). Reason: True developmental context of Kdr; non-core. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0003416 endochondral bone growth | IMP PMID:14612527 Pharmacological characterization of CP-547,632, a novel vasc... | UNDECIDED | Summary: IMP using CP-547,632, a small-molecule VEGFR-2 inhibitor. Reason: Only the abstract is available and it does not describe bone growth; the compound inhibits FGFR kinase as potently as VEGFR-2, so a growth-plate phenotype cannot be attributed to Kdr from the visible evidence. Supporting Evidence: PMID:14612527 was identified as a potent inhibitor of the VEGFR-2 and basic fibroblast growth factor (FGF) kinases |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Kdr is a receptor tyrosine kinase; protein kinase activity is true but generic. Reason: The kinase activity of Kdr is that of a ligand-activated transmembrane receptor tyrosine kinase for VEGFs. GO:0005021 vascular endothelial growth factor receptor activity is an is_a descendant of this term and is already carried by the gene (IBA, IMP, ISO), so the row is refined to it. Proposed replacements: vascular endothelial growth factor receptor activity Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues UniProtKB:O08775 Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Kdr is a receptor tyrosine kinase; protein tyrosine kinase activity is true but generic. Reason: The kinase activity of Kdr is that of a ligand-activated transmembrane receptor tyrosine kinase for VEGFs. GO:0005021 vascular endothelial growth factor receptor activity is an is_a descendant of this term and is already carried by the gene (IBA, IMP, ISO), so the row is refined to it. Proposed replacements: vascular endothelial growth factor receptor activity Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues UniProtKB:O08775 Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| GO:0004713 protein tyrosine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Kdr is a receptor tyrosine kinase; protein tyrosine kinase activity is true but generic. Reason: The kinase activity of Kdr is that of a ligand-activated transmembrane receptor tyrosine kinase for VEGFs. GO:0005021 vascular endothelial growth factor receptor activity is an is_a descendant of this term and is already carried by the gene (IBA, IMP, ISO), so the row is refined to it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Donor KDR is a VEGF-activated receptor tyrosine kinase; the transferred kinase term is true but less specific than VEGF receptor activity. Proposed replacements: vascular endothelial growth factor receptor activity Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues UniProtKB:O08775 Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| GO:0004713 protein tyrosine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Kdr is a receptor tyrosine kinase; protein tyrosine kinase activity is true but generic. Reason: The kinase activity of Kdr is that of a ligand-activated transmembrane receptor tyrosine kinase for VEGFs. GO:0005021 vascular endothelial growth factor receptor activity is an is_a descendant of this term and is already carried by the gene (IBA, IMP, ISO), so the row is refined to it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P35968 SUPPORTS TRANSFER Donor KDR is a VEGF-activated receptor tyrosine kinase; the transferred kinase term is true but less specific than VEGF receptor activity. Proposed replacements: vascular endothelial growth factor receptor activity Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues UniProtKB:O08775 Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Kdr is a receptor tyrosine kinase; transmembrane receptor protein tyrosine kinase activity is true but generic. Reason: The kinase activity of Kdr is that of a ligand-activated transmembrane receptor tyrosine kinase for VEGFs. GO:0005021 vascular endothelial growth factor receptor activity is an is_a descendant of this term and is already carried by the gene (IBA, IMP, ISO), so the row is refined to it. Proposed replacements: vascular endothelial growth factor receptor activity Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues UniProtKB:O08775 Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| GO:0005021 vascular endothelial growth factor receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: VEGF receptor activity is the defining activity of Kdr: VEGFA/C/D binding induces dimerization and trans-autophosphorylation of the kinase. Reason: Core function, consistent with rat experimental data (PMID:9442048, PMID:9160888) and the IBA family node. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues PMID:9442048 VEGF induced a biphasic increase of cytoplasmic calcium with both forms in HK 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional |
| GO:0005021 vascular endothelial growth factor receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: VEGF receptor activity is the defining activity of Kdr: VEGFA/C/D binding induces dimerization and trans-autophosphorylation of the kinase. Reason: Core function, consistent with rat experimental data (PMID:9442048, PMID:9160888) and the IBA family node. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues PMID:9442048 VEGF induced a biphasic increase of cytoplasmic calcium with both forms in HK 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional |
| GO:0005021 vascular endothelial growth factor receptor activity | IMP PMID:15785231 VEGF and VEGF receptor expression after experimental brain c... | ACCEPT | Summary: Abstract reports Flk-1 mRNA and protein in vessels after brain contusion; the receptor-activity IMP must rest on full-text experiments not visible in the abstract. Reason: The abstract is expression-focused, but the function is the established core activity of Kdr, so the curator's annotation is accepted rather than second-guessed from an abstract. Supporting Evidence: PMID:15785231 Flt-1 and Flk-1 mRNA and protein were detected in vessels adjacent to the lesion from 1 day after injury throughout day 6 after injury UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0005021 vascular endothelial growth factor receptor activity | IMP PMID:9442048 Two functional forms of vascular endothelial growth factor r... | ACCEPT | Summary: Rat Flk-1 cDNAs (full-length and a C-terminally truncated form) expressed in HEK293 cells mediate VEGF-induced Ca2+ signalling, showing functional VEGF receptor activity of the rat protein. Reason: Direct rat evidence that the cloned receptor binds VEGF and transduces a signal; this is the core activity. Supporting Evidence: PMID:9442048 VEGF induced a biphasic increase of cytoplasmic calcium with both forms in HK 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0005021 vascular endothelial growth factor receptor activity | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor activity is the defining activity of Kdr: VEGFA/C/D binding induces dimerization and trans-autophosphorylation of the kinase. Reason: Core function, consistent with rat experimental data (PMID:9442048, PMID:9160888) and the IBA family node. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues PMID:9442048 VEGF induced a biphasic increase of cytoplasmic calcium with both forms in HK 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional |
| GO:0005021 vascular endothelial growth factor receptor activity | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor activity is the defining activity of Kdr: VEGFA/C/D binding induces dimerization and trans-autophosphorylation of the kinase. Reason: Core function, consistent with rat experimental data (PMID:9442048, PMID:9160888) and the IBA family node. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues PMID:9442048 VEGF induced a biphasic increase of cytoplasmic calcium with both forms in HK 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional |
| GO:0005178 integrin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Human KDR associates with integrins (alphavbeta3; IPI PMID:10022831, PMID:30873824), which co-operate with VEGFR2 in endothelial adhesion and migration. Reason: Supported in the donor but peripheral to the receptor's core activity. Supporting Evidence: UniProtKB:O08775 Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding by the tyrosine kinase domain, inferred from InterPro kinase signatures. Reason: True and required for catalysis, but subsumed in the kinase activity; kept as non-core. Supporting Evidence: UniProtKB:O08775 Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: VEGF stimulation has been reported to translocate KDR to the nucleus/nuclear envelope. Reason: Reported by similarity to human KDR; peripheral to the receptor function. Supporting Evidence: UniProtKB:O08775 VEGFA binding triggers internalization and translocation to the nucleus |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGF stimulation has been reported to translocate KDR to the nucleus/nuclear envelope. Reason: Reported by similarity to human KDR; peripheral to the receptor function. Supporting Evidence: UniProtKB:O08775 VEGFA binding triggers internalization and translocation to the nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Intracellular (cytoplasmic) pools of Kdr reflect biosynthesis and internalisation. Reason: True in the broad sense; non-core. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Intracellular (cytoplasmic) pools of Kdr reflect biosynthesis and internalisation. Reason: True in the broad sense; non-core. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0005768 endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGF-bound Kdr is internalised and trafficked through endosomes, where it continues to signal before recycling or degradation. Reason: Endosomal trafficking is well documented for VEGFR2 and modulates signalling, but the core activity is at the plasma membrane. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0005769 early endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: VEGF-bound Kdr is internalised and trafficked through endosomes, where it continues to signal before recycling or degradation. Reason: Endosomal trafficking is well documented for VEGFR2 and modulates signalling, but the core activity is at the plasma membrane. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0005769 early endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGF-bound Kdr is internalised and trafficked through endosomes, where it continues to signal before recycling or degradation. Reason: Endosomal trafficking is well documented for VEGFR2 and modulates signalling, but the core activity is at the plasma membrane. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Kdr is detected in the ER (biosynthetic pool; colocalisation with ERN1 and XBP1). Reason: Root organelle term (projects/ORGANELLES.md): the ISO/ISS/IEA rows rest on human KDR ER localisation (UniProt, PMID-backed) and on the glycosylation-dependent maturation of the receptor; the ER claim holds but is peripheral, so it is kept as non-core. Supporting Evidence: UniProtKB:O08775 Colocalizes with ERN1 and XBP1 in the endoplasmic reticulum in endothelial cells PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr is detected in the ER (biosynthetic pool; colocalisation with ERN1 and XBP1). Reason: Root organelle term (projects/ORGANELLES.md): the ISO/ISS/IEA rows rest on human KDR ER localisation (UniProt, PMID-backed) and on the glycosylation-dependent maturation of the receptor; the ER claim holds but is peripheral, so it is kept as non-core. Supporting Evidence: UniProtKB:O08775 Colocalizes with ERN1 and XBP1 in the endoplasmic reticulum in endothelial cells PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Kdr is detected in the ER (biosynthetic pool; colocalisation with ERN1 and XBP1). Reason: Root organelle term (projects/ORGANELLES.md): the ISO/ISS/IEA rows rest on human KDR ER localisation (UniProt, PMID-backed) and on the glycosylation-dependent maturation of the receptor; the ER claim holds but is peripheral, so it is kept as non-core. Supporting Evidence: UniProtKB:O08775 Colocalizes with ERN1 and XBP1 in the endoplasmic reticulum in endothelial cells PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005794 Golgi apparatus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Human KDR detected in the Golgi apparatus (IDA PMID:23262137), consistent with glycan maturation en route to the cell surface. Reason: Root organelle term: the donor is a direct IDA; the Golgi pool is biosynthetic transit, peripheral to function. Supporting Evidence: PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005829 cytosol | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cytosol transferred from human KDR, whose cytosol annotation is an HPA antibody-staining IDA. Reason: Kdr is a transmembrane receptor; its kinase domain faces the cytosol but the protein is not a cytosolic resident. A diffuse HPA immunofluorescence signal does not establish a soluble cytosolic pool. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P35968 SOURCE WEAK OR INFERRED Human donor cytosol row is HPA immunofluorescence (GO_REF:0000052). Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein file:rat/Kdr/Kdr-deep-research-manual.md Human KDR: cytosol is an HPA immunofluorescence IDA |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Kdr is a single-pass type I plasma membrane receptor where ligand binding and kinase activation occur. Reason: Plasma membrane is where the core VEGF receptor activity is performed. Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Kdr is a single-pass type I plasma membrane receptor where ligand binding and kinase activation occur. Reason: Plasma membrane is where the core VEGF receptor activity is performed. Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr is a single-pass type I plasma membrane receptor where ligand binding and kinase activation occur. Reason: Plasma membrane is where the core VEGF receptor activity is performed. Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr is a single-pass type I plasma membrane receptor where ligand binding and kinase activation occur. Reason: Plasma membrane is where the core VEGF receptor activity is performed. Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr is a single-pass type I plasma membrane receptor where ligand binding and kinase activation occur. Reason: Plasma membrane is where the core VEGF receptor activity is performed. Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: Kdr is a receptor tyrosine kinase that initiates cell surface RTK signalling. Reason: Correct but general; the specific pathway is GO:0036324 VEGFR-2 signaling pathway, a descendant already annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: FB:FBgn0003366 SUPPORTS TRANSFER Family-level RTK signalling node; sound, but the receptor-specific descendant is supported. FB:FBgn0003731 SUPPORTS TRANSFER Family-level RTK signalling node; sound, but the receptor-specific descendant is supported. FB:FBgn0032006 SUPPORTS TRANSFER Family-level RTK signalling node; sound, but the receptor-specific descendant is supported. FB:FBgn0040505 SUPPORTS TRANSFER Family-level RTK signalling node; sound, but the receptor-specific descendant is supported. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Kdr is a receptor tyrosine kinase that initiates cell surface RTK signalling. Reason: Correct but general; the specific pathway is GO:0036324 VEGFR-2 signaling pathway, a descendant already annotated. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IMP PMID:18221855 Vascular endothelial growth factor (VEGF) signaling regulate... | KEEP AS NON CORE | Summary: VEGF raises cytosolic Ca2+ via VEGFR2 in rat hippocampal neurons. Reason: Downstream of PLCG1 activation; non-core. Supporting Evidence: PMID:18221855 A brief (10 min) application of recombinant VEGF165 to neurons elicited a slow rise in cytosolic Ca2+ in a VEGFR2 dependent manner UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kdr signalling promotes cell proliferation, principally but not only of endothelial cells. Reason: Kdr is mitogenic for endothelial cells and, in rat, also for glioma cells and neural progenitors (PMID:17881084, PMID:17360578), so the generic term is as precise as the combined evidence allows; the endothelial outcome is captured separately by GO:0001938 (accepted). Kept as non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:17881084 Heparin affin regulatory peptide/pleiotrophin negatively aff... | KEEP AS NON CORE | Summary: VEGF-VEGFR2 signalling drives proliferation of rat C6 glioma cells (VEGFR2 inhibitor SU1496). Reason: Kdr's mitogenic effect is not restricted to endothelium (glioma cells here; neural progenitors, PMID:17360578), so the generic term is as precise as the combined evidence warrants. The endothelial case is captured separately by GO:0001938 (accepted). Supporting Evidence: PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling promotes cell proliferation, principally but not only of endothelial cells. Reason: Kdr is mitogenic for endothelial cells and, in rat, also for glioma cells and neural progenitors (PMID:17881084, PMID:17360578), so the generic term is as precise as the combined evidence allows; the endothelial outcome is captured separately by GO:0001938 (accepted). Kept as non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0008360 regulation of cell shape | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling reorganises the actin cytoskeleton and cell shape. Reason: Supported; non-core. Supporting Evidence: UniProtKB:O08775 Promotes reorganization of the actin cytoskeleton |
| GO:0008406 gonad development | IEA GO_REF:0000117 | MODIFY | Summary: Gonad development (ARBA). Reason: The supported rat evidence is for male gonad development (GO:0008584, is_a gonad development), already annotated. Proposed replacements: male gonad development Supporting Evidence: PMID:16672722 inhibited cord formation in E13 testis cultures with 90% reduced vascular density |
| GO:0008584 male gonad development | IDA PMID:16672722 Vascular endothelial growth factor and kinase domain region ... | KEEP AS NON CORE | Summary: VEGFR kinase inhibitors block seminiferous cord formation and vascularization of cultured E13 rat testes; KDR localises to germ and interstitial cells. Reason: Organ-development context, non-core. Supporting Evidence: PMID:16672722 VEGFA protein was localized to Sertoli cells at cord formation and KDR to germ and interstitial cells PMID:16672722 inhibited cord formation in E13 testis cultures with 90% reduced vascular density |
| GO:0009410 response to xenobiotic stimulus | IMP PMID:17360578 VEGF is an essential mediator of the neurogenic and behavior... | MARK AS OVER ANNOTATED | Summary: Rat IMP: Flk-1 signalling is required for antidepressant-induced hippocampal cell proliferation and behavioural responses. Reason: Kdr does not respond to the drug; antidepressants induce VEGF, which then signals through Flk-1. 'Response to xenobiotic stimulus' conflates a pharmacological experimental context with the receptor's role. Supporting Evidence: PMID:17360578 We find that VEGF signaling through the Flk-1 receptor is required for antidepressant-induced cell proliferation |
| GO:0009897 external side of plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ectodomain on the external face of the plasma membrane (mouse IDA donors). Reason: Topologically correct for a type I receptor; finer than needed, retained as non-core. Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein |
| GO:0009967 positive regulation of signal transduction | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Positive regulation of signal transduction (ARBA). Reason: Kdr is the receptor that initiates VEGF signalling, a pathway member rather than a regulator of signal transduction; the vague regulatory term adds nothing to the VEGFR-2 pathway annotation. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0009986 cell surface | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cell-surface detection of Kdr (mouse donors). Reason: Consistent with plasma membrane residence of the mature receptor; non-core. Supporting Evidence: PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface |
| GO:0010595 positive regulation of endothelial cell migration | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling drives endothelial cell migration and chemotaxis, including tip-cell migration in sprouting angiogenesis. Reason: Core cellular outcome of the receptor. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression transferred from human KDR (IDA PMID:26879375, an H2S study). Reason: An unspecified gene-expression effect is a downstream, indirect consequence of receptor signalling and uninformative for Kdr. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P35968 SOURCE WEAK OR INFERRED Donor IDA from PMID:26879375 not read; likely a readout of signalling, not a direct role in gene regulation. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0015026 coreceptor activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Transferred from mouse Kdr IGI with SEMA3E (PMID:25985275), where VEGFR2 acts with PlexinD1 in Sema3E signalling. Reason: VEGFR2 cooperating as a co-receptor in Sema3E-PlexinD1 signalling is a context-specific role reported in mouse; plausible for rat but peripheral to the primary VEGF receptor function. Supporting Evidence: UniProtKB:O08775 Modulates FLT1 and FLT4 signaling by forming heterodimers file:rat/Kdr/Kdr-deep-research-manual.md coreceptor activity and semaphorin-plexin signalling rest on an IGI with |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Membrane location inferred from the VEGFR InterPro signature. Reason: Correct but generic; the receptor acts at the plasma membrane (GO:0005886), which the gene already carries. Proposed replacements: plasma membrane Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein PMID:9160888 after further glycosylation a mature 230 kDa was expressed on the cell surface |
| GO:0016239 positive regulation of macroautophagy | ISO GO_REF:0000121 | UNDECIDED | Summary: positive regulation of macroautophagy transferred from a human KDR row made by MGI as IGI (PMID:23798385, acts upstream). Reason: The donor genetic-interaction paper was not available; a mitochondrial/autophagy phenotype could reflect any of many downstream effects of VEGFR2 signalling and cannot be assessed here. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P35968 UNRESOLVED Donor IGI (PMID:23798385, assigned by MGI) not read. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0016477 cell migration | IBA GO_REF:0000033 | MODIFY | Summary: Cell migration (IBA family node / mouse). Reason: Correct but general; the cell type whose migration Kdr drives is endothelial (GO:0043542 endothelial cell migration, is_a cell migration). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:95558 SUPPORTS TRANSFER Donor evidence concerns endothelial migration downstream of VEGFR2. MGI:MGI:96677 SUPPORTS TRANSFER Donor evidence concerns endothelial migration downstream of VEGFR2. MGI:MGI:96683 SUPPORTS TRANSFER Donor evidence concerns endothelial migration downstream of VEGFR2. MGI:MGI:97530 SUPPORTS TRANSFER Donor evidence concerns endothelial migration downstream of VEGFR2. Proposed replacements: endothelial cell migration Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0016477 cell migration | ISO GO_REF:0000121 | MODIFY | Summary: Cell migration (IBA family node / mouse). Reason: Correct but general; the cell type whose migration Kdr drives is endothelial (GO:0043542 endothelial cell migration, is_a cell migration). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Donor evidence concerns endothelial migration downstream of VEGFR2. Proposed replacements: endothelial cell migration Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0018108 peptidyl-tyrosine phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr autophosphorylates and phosphorylates PLCG1 on tyrosine. Reason: Direct consequence of its kinase activity, supported by rat PLC-gamma phosphorylation data. Supporting Evidence: UniProtKB:O08775 Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC PMID:9160888 As a major substrate of KDR/Flk-1, PLC-gamma was found to be rapidly tyrosine-phosphorylated and associated with KDR/Flk-1 both in endothelial cells and NIH3T3 cells |
| GO:0019838 growth factor binding | IBA GO_REF:0000033 | MODIFY | Summary: Kdr binds VEGF family growth factors (VEGFA, VEGFC, VEGFD) through Ig-like domains 2-3. Reason: Growth factor binding is correct but general; GO:0038085 vascular endothelial growth factor binding is its is_a descendant and is already annotated to the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Donor binding evidence concerns VEGF family ligands; growth factor binding is the less specific parent. MGI:MGI:97530 SUPPORTS TRANSFER Donor binding evidence concerns VEGF family ligands; growth factor binding is the less specific parent. PANTHER:PTN004704336 SUPPORTS TRANSFER Donor binding evidence concerns VEGF family ligands; growth factor binding is the less specific parent. RGD:2621 SUPPORTS TRANSFER Donor binding evidence concerns VEGF family ligands; growth factor binding is the less specific parent. Proposed replacements: vascular endothelial growth factor binding Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0019838 growth factor binding | IEA GO_REF:0000120 | MODIFY | Summary: Kdr binds VEGF family growth factors (VEGFA, VEGFC, VEGFD) through Ig-like domains 2-3. Reason: Growth factor binding is correct but general; GO:0038085 vascular endothelial growth factor binding is its is_a descendant and is already annotated to the gene. Proposed replacements: vascular endothelial growth factor binding Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0019838 growth factor binding | IMP PMID:9442048 Two functional forms of vascular endothelial growth factor r... | MODIFY | Summary: Kdr binds VEGF family growth factors (VEGFA, VEGFC, VEGFD) through Ig-like domains 2-3. Reason: Growth factor binding is correct but general; GO:0038085 vascular endothelial growth factor binding is its is_a descendant and is already annotated to the gene. Proposed replacements: vascular endothelial growth factor binding Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0019838 growth factor binding | IPI PMID:9160888 The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activ... | MODIFY | Summary: Kdr binds VEGF family growth factors (VEGFA, VEGFC, VEGFD) through Ig-like domains 2-3. Reason: Growth factor binding is correct but general; GO:0038085 vascular endothelial growth factor binding is its is_a descendant and is already annotated to the gene. The WITH entity RGD:731072 is human VEGFA (RGD record), so the IPI is VEGF binding. Proposed replacements: vascular endothelial growth factor binding Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0019838 growth factor binding | ISO GO_REF:0000121 | MODIFY | Summary: Kdr binds VEGF family growth factors (VEGFA, VEGFC, VEGFD) through Ig-like domains 2-3. Reason: Growth factor binding is correct but general; GO:0038085 vascular endothelial growth factor binding is its is_a descendant and is already annotated to the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Donor binding evidence concerns VEGF family ligands; growth factor binding is the less specific parent. Proposed replacements: vascular endothelial growth factor binding Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0019838 growth factor binding | ISO GO_REF:0000121 | MODIFY | Summary: Kdr binds VEGF family growth factors (VEGFA, VEGFC, VEGFD) through Ig-like domains 2-3. Reason: Growth factor binding is correct but general; GO:0038085 vascular endothelial growth factor binding is its is_a descendant and is already annotated to the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P35968 SUPPORTS TRANSFER Donor binding evidence concerns VEGF family ligands; growth factor binding is the less specific parent. Proposed replacements: vascular endothelial growth factor binding Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0019955 cytokine binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Transferred from a mouse IPI with gremlin-1 (Grem1, O70326; PMID:20660291), a BMP antagonist that also acts as a VEGFR2 agonist. Reason: The donor binding partner is gremlin-1, classed as a cytokine, not VEGF, so the row should not be collapsed into VEGF binding. Non-canonical ligand binding is peripheral to the VEGF receptor function. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD file:rat/Kdr/Kdr-deep-research-manual.md cytokine binding is an IPI with gremlin-1 (Grem1, O70326, |
| GO:0030054 cell junction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr localizes to endothelial cell-cell junctions with VE-cadherin/RAP1A. Reason: Supported but peripheral location. Supporting Evidence: UniProtKB:O08775 Localized with RAP1A at cell-cell junctions |
| GO:0030054 cell junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Kdr localizes to endothelial cell-cell junctions with VE-cadherin/RAP1A. Reason: Supported but peripheral location. Supporting Evidence: UniProtKB:O08775 Localized with RAP1A at cell-cell junctions |
| GO:0030097 hemopoiesis | ISO GO_REF:0000121 | MODIFY | Summary: Hemopoiesis transferred from mouse Kdr (acts upstream). Reason: The supported claim is embryonic hemopoiesis (GO:0035162), an is_a descendant already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Mouse Kdr genetics show a requirement in embryonic hematopoiesis; the parent term is less informative. Proposed replacements: embryonic hemopoiesis Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0030324 lung development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lung development from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0030335 positive regulation of cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kdr signalling promotes cell migration, chiefly but not only of endothelial cells. Reason: Kdr drives endothelial migration and, in rat, also glioma cell migration (PMID:17881084), so the generic term is as precise as the combined evidence warrants; the endothelial case is captured separately by GO:0010595 (accepted). Kept as non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Kdr signalling promotes cell migration, chiefly but not only of endothelial cells. Reason: Kdr drives endothelial migration and, in rat, also glioma cell migration (PMID:17881084), so the generic term is as precise as the combined evidence warrants; the endothelial case is captured separately by GO:0010595 (accepted). Kept as non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0030335 positive regulation of cell migration | IMP PMID:17881084 Heparin affin regulatory peptide/pleiotrophin negatively aff... | KEEP AS NON CORE | Summary: VEGFR2 inhibition blocks migration of rat C6 glioma cells. Reason: Non-endothelial context, so the generic term is as specific as the combined evidence allows; endothelial migration is captured by GO:0010595 (accepted). Supporting Evidence: PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling promotes cell migration, chiefly but not only of endothelial cells. Reason: Kdr drives endothelial migration and, in rat, also glioma cell migration (PMID:17881084), so the generic term is as precise as the combined evidence warrants; the endothelial case is captured separately by GO:0010595 (accepted). Kept as non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells PMID:17881084 VEGF induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity |
| GO:0030513 positive regulation of BMP signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of BMP signalling transferred from a mouse IDA (PMID:20406889). Reason: Donor paper not read; plausible crosstalk (VEGFR2 and BMP pathways in endothelium) but peripheral. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: VEGF-bound Kdr is internalised and trafficked through endosomes, where it continues to signal before recycling or degradation. Reason: Endosomal trafficking is well documented for VEGFR2 and modulates signalling, but the core activity is at the plasma membrane. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0031965 nuclear membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGF stimulation has been reported to translocate KDR to the nucleus/nuclear envelope. Reason: Reported by similarity to human KDR; peripheral to the receptor function. Supporting Evidence: UniProtKB:O08775 VEGFA binding triggers internalization and translocation to the nucleus |
| GO:0032008 positive regulation of TOR signaling | IMP PMID:18221855 Vascular endothelial growth factor (VEGF) signaling regulate... | KEEP AS NON CORE | Summary: VEGF activates mTOR in rat hippocampal neurons in a VEGFR2-dependent manner. Reason: Neuronal downstream output; non-core. Supporting Evidence: PMID:18221855 as well as extracellular signal-regulated protein kinase and mammalian target of rapamycin-all in a VEGFR2 dependent manner |
| GO:0035162 embryonic hemopoiesis | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr is required for embryonic hematopoiesis (mouse Flk1 knockout). Reason: UniProt function statement and mouse donor genetics support this developmental role. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0035162 embryonic hemopoiesis | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr is required for embryonic hematopoiesis (mouse Flk1 knockout). Reason: UniProt function statement and mouse donor genetics support this developmental role. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr mediates the cellular response to VEGF. Reason: Directly reflects the receptor function. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr mediates the cellular response to VEGF. Reason: Directly reflects the receptor function. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr initiates the VEGFR-2 signalling pathway. Reason: Core process. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr initiates the VEGFR-2 signalling pathway. Reason: Core process. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:0038084 vascular endothelial growth factor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF signalling pathway initiated by VEGF binding to Kdr. Reason: Core process; Kdr is the main signalling VEGF receptor. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0038084 vascular endothelial growth factor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF signalling pathway initiated by VEGF binding to Kdr. Reason: Core process; Kdr is the main signalling VEGF receptor. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0038085 vascular endothelial growth factor binding | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr binds VEGFA, VEGFC and VEGFD; the human isoform 2 (soluble) also binds VEGF, consistent with a decoy function. Reason: Ligand binding is an intrinsic part of the core VEGF receptor activity. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0038085 vascular endothelial growth factor binding | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr binds VEGFA, VEGFC and VEGFD; the human isoform 2 (soluble) also binds VEGF, consistent with a decoy function. Reason: Ligand binding is an intrinsic part of the core VEGF receptor activity. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| GO:0042311 vasodilation | IGI PMID:12052848 KDR (VEGF receptor 2) is the major mediator for the hypotens... | KEEP AS NON CORE | Summary: VEGF-induced vasorelaxation of rat vessels is mediated mainly by KDR. Reason: Supported rat physiology; non-core. Supporting Evidence: PMID:12052848 VEGF and KDR-selective mutant induced more potent vasorelaxation than Flt-selective mutant |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: KDR homodimerises upon binding dimeric VEGF ligands (human IPI rows). Reason: Homodimerization is a mechanistic step of receptor activation; identical protein binding is retained as non-core. Supporting Evidence: UniProtKB:O08775 Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands |
| GO:0043025 neuronal cell body | IDA PMID:11934468 Angiogenic and astroglial responses to vascular endothelial ... | KEEP AS NON CORE | Summary: Flk-1 immunoreactivity in neuronal somata and processes of adult rat brain after VEGF delivery. Reason: Direct rat observation from the abstract; neuronal Kdr mediates neurotrophic VEGF effects but this is not the core vascular location. Supporting Evidence: PMID:11934468 flk-1 was expressed in vascular endothelium but predominantly in neuronal somata and processes adjacent to the delivery site |
| GO:0043129 surfactant homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Surfactant homeostasis from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0043235 signaling receptor complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Ligand-bound Kdr forms a signalling receptor complex (homo- or heterodimers with FLT1/FLT4, with neuropilin co-receptors). Reason: The family-level IBA is sound; the complex is the active receptor dimer, retained as non-core. Supporting Evidence: UniProtKB:O08775 Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands UniProtKB:O08775 Modulates FLT1 and FLT4 signaling by forming heterodimers |
| GO:0043408 regulation of MAPK cascade | IBA GO_REF:0000033 | MODIFY | Summary: Kdr regulates MAPK signalling. Reason: The direction is established: Kdr activates the MAPK/ERK cascade. GO:0043410 positive regulation of MAPK cascade is the descendant already annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002814441 SUPPORTS TRANSFER Donor human KDR activates ERK1/2. UniProtKB:P35968 SUPPORTS TRANSFER Donor human KDR activates ERK1/2. Proposed replacements: positive regulation of MAPK cascade Supporting Evidence: UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:0043410 positive regulation of MAPK cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling activates the MAPK/ERK1/2 cascade. Reason: Well-supported downstream output; non-core relative to receptor activity. Supporting Evidence: UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Kdr signalling activates the MAPK/ERK1/2 cascade. Reason: Well-supported downstream output; non-core relative to receptor activity. Supporting Evidence: UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Kdr mediates VEGF neuroprotection (rat spinal motor neurons under hypoxia). Reason: Supported by rat IMP; non-core neuronal role. Supporting Evidence: PMID:15780476 These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways |
| GO:0043524 negative regulation of neuron apoptotic process | IMP PMID:15780476 Reduction of a vascular endothelial growth factor receptor, ... | KEEP AS NON CORE | Summary: Kdr mediates VEGF neuroprotection (rat spinal motor neurons under hypoxia). Reason: Supported by rat IMP; non-core neuronal role. Supporting Evidence: PMID:15780476 These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways |
| GO:0043524 negative regulation of neuron apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr mediates VEGF neuroprotection (rat spinal motor neurons under hypoxia). Reason: Supported by rat IMP; non-core neuronal role. Supporting Evidence: PMID:15780476 These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling drives endothelial cell migration and chemotaxis, including tip-cell migration in sprouting angiogenesis. Reason: Core cellular outcome of the receptor. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0045121 membrane raft | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr is found in caveolae/lipid rafts. Reason: Supported sub-domain of the plasma membrane; non-core. Supporting Evidence: UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface |
| GO:0045165 cell fate commitment | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cell fate commitment from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0045296 cadherin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Human KDR associates with VE-cadherin junctional complexes (IPI PMID:11950700, PMID:25893857). Reason: Junctional association regulates VEGFR2 signalling and internalisation but is not its core activity. Supporting Evidence: UniProtKB:O08775 Localized with RAP1A at cell-cell junctions |
| GO:0045446 endothelial cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kdr signalling is required for endothelial cell differentiation from mesoderm (mouse). Reason: Supported developmental role; non-core relative to the receptor signalling function. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0045446 endothelial cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling is required for endothelial cell differentiation from mesoderm (mouse). Reason: Supported developmental role; non-core relative to the receptor signalling function. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0045766 positive regulation of angiogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: VEGF-Kdr signalling promotes angiogenesis; rat KDR kinase inhibition blocks ocular neovascularization. Reason: Core; consistent across IBA, IDA, ISO and IEA rows. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis PMID:15951738 Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:15951738 Inhibition of retinal and choroidal neovascularization by a ... | ACCEPT | Summary: VEGF-Kdr signalling promotes angiogenesis; rat KDR kinase inhibition blocks ocular neovascularization. Reason: Core; consistent across IBA, IDA, ISO and IEA rows. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis PMID:15951738 Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization |
| GO:0045766 positive regulation of angiogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: VEGF-Kdr signalling promotes angiogenesis; rat KDR kinase inhibition blocks ocular neovascularization. Reason: Core; consistent across IBA, IDA, ISO and IEA rows. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis PMID:15951738 Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling promotes angiogenesis; rat KDR kinase inhibition blocks ocular neovascularization. Reason: Core; consistent across IBA, IDA, ISO and IEA rows. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis PMID:15951738 Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling promotes angiogenesis; rat KDR kinase inhibition blocks ocular neovascularization. Reason: Core; consistent across IBA, IDA, ISO and IEA rows. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis PMID:15951738 Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IEA GO_REF:0000120 | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:18221855 Vascular endothelial growth factor (VEGF) signaling regulate... | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: PMID:18221855 A brief (10 min) application of recombinant VEGF165 to neurons elicited a slow rise in cytosolic Ca2+ in a VEGFR2 dependent manner PMID:18221855 as well as extracellular signal-regulated protein kinase and mammalian target of rapamycin-all in a VEGFR2 dependent manner |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:18614764 Astrocyte responses to injury: VEGF simultaneously modulates... | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:9442048 Two functional forms of vascular endothelial growth factor r... | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: PMID:9442048 VEGF induced a biphasic increase of cytoplasmic calcium with both forms in HK 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | ISO GO_REF:0000121 | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Donor evidence is VEGFR2-mediated signalling; the general VEGFR pathway is the parent of the VEGFR-2 specific term. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | ISO GO_REF:0000121 | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P35968 SUPPORTS TRANSFER Donor evidence is VEGFR2-mediated signalling; the general VEGFR pathway is the parent of the VEGFR-2 specific term. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | ISS GO_REF:0000024 | MODIFY | Summary: Kdr transduces VEGF signals; the pathway it initiates is specifically the VEGFR-2 pathway. Reason: Correct but general: GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway is the is_a descendant that names this receptor and is already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P35968 SUPPORTS TRANSFER Donor evidence is VEGFR2-mediated signalling; the general VEGFR pathway is the parent of the VEGFR-2 specific term. Proposed replacements: vascular endothelial growth factor receptor-2 signaling pathway Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C |
| GO:0048170 positive regulation of long-term neuronal synaptic plasticity | IMP PMID:18221855 Vascular endothelial growth factor (VEGF) signaling regulate... | KEEP AS NON CORE | Summary: Brief VEGF stimulation produces VEGFR2-dependent long-term synaptic enhancement in rat hippocampus. Reason: Neuronal context; non-core. Supporting Evidence: PMID:18221855 The same brief stimulus with VEGF led to long-term synaptic enhancement dependent on protein synthesis |
| GO:0048286 lung alveolus development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lung alveolus development from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0048469 cell maturation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cell maturation, from a mouse lung-maturation study (PMID:12053176, acts upstream). Reason: The donor phenotype is fetal lung (type II pneumocyte) maturation downstream of VEGF signalling; generic 'cell maturation' is an indirect, uninformative consequence for a receptor tyrosine kinase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96683 SOURCE WEAK OR INFERRED Mouse IMP records a downstream developmental consequence, not a step performed by Kdr. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0048597 post-embryonic camera-type eye morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Post-embryonic camera-type eye morphogenesis from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0048678 response to axon injury | IEP PMID:20187850 Multiple receptor tyrosine kinases are expressed in adult ra... | MARK AS OVER ANNOTATED | Summary: IEP from RGC single-cell RT-PCR after optic nerve transection. Reason: Full text shows Vegfr-2 mRNA was essentially unchanged after injury except a transient decrease at 6 h; expression alone does not show Kdr participates in a response to axon injury. Supporting Evidence: PMID:20187850 The regulation after injury was not significantly altered from normal levels except at 6 hours after injury, when there was a decrease. |
| GO:0048754 branching morphogenesis of an epithelial tube | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Branching morphogenesis of an epithelial tube from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0048812 neuron projection morphogenesis | IMP PMID:16329123 Vascular endothelial growth factor stimulates neurite outgro... | KEEP AS NON CORE | Summary: VEGF-induced neurite outgrowth from rat cortical neurons depends on VEGFR2 and Rho/ROK. Reason: Neuronal context; non-core. Supporting Evidence: PMID:16329123 VEGF promotes neurite outgrowth from cerebral cortical neurons by interacting with VEGFR2 and activating Rho/ROK signaling pathways |
| GO:0050679 positive regulation of epithelial cell proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of epithelial cell proliferation from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0050679 positive regulation of epithelial cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of epithelial cell proliferation from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:0050769 positive regulation of neurogenesis | IEP PMID:15258583 VEGF links hippocampal activity with neurogenesis, learning ... | KEEP AS NON CORE | Summary: Dominant-negative KDR inhibits basal and VEGF-enhanced hippocampal neurogenesis in adult rats. Reason: The process claim is supported, but the evidence in the abstract is a loss-of-function experiment (dominant-negative KDR), not expression pattern; IMP would be the appropriate code. Supporting Evidence: PMID:15258583 Expression of a dominant-negative mutant KDR inhibited basal neurogenesis and impaired learning |
| GO:0050850 positive regulation of calcium-mediated signaling | IMP PMID:18221855 Vascular endothelial growth factor (VEGF) signaling regulate... | KEEP AS NON CORE | Summary: VEGFR2-dependent Ca2+ signalling and CaMKII activation in rat neurons. Reason: Downstream output; non-core. Supporting Evidence: PMID:18221855 A brief (10 min) application of recombinant VEGF165 to neurons elicited a slow rise in cytosolic Ca2+ in a VEGFR2 dependent manner |
| GO:0050927 positive regulation of positive chemotaxis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGF-induced chemotaxis via KDR (human IDA PMID:7929439). Reason: Supported; overlaps the endothelial chemotaxis term, kept non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0051894 positive regulation of focal adhesion assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr promotes FAK activation and focal adhesion assembly. Reason: Supported; non-core. Supporting Evidence: UniProtKB:O08775 Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1 |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:18221855 Vascular endothelial growth factor (VEGF) signaling regulate... | KEEP AS NON CORE | Summary: Kdr signalling activates PI3K-AKT. Reason: Downstream output of the receptor; non-core. Supporting Evidence: PMID:18221855 as well as extracellular signal-regulated protein kinase and mammalian target of rapamycin-all in a VEGFR2 dependent manner |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling activates PI3K-AKT. Reason: Downstream output of the receptor; non-core. Supporting Evidence: UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway UniProtKB:O08775 Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1 |
| GO:0051901 positive regulation of mitochondrial depolarization | ISO GO_REF:0000121 | UNDECIDED | Summary: positive regulation of mitochondrial depolarization transferred from a human KDR row made by MGI as IGI (PMID:23798385, acts upstream). Reason: The donor genetic-interaction paper was not available; a mitochondrial/autophagy phenotype could reflect any of many downstream effects of VEGFR2 signalling and cannot be assessed here. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P35968 UNRESOLVED Donor IGI (PMID:23798385, assigned by MGI) not read. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0055074 calcium ion homeostasis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Calcium ion homeostasis transferred from mouse IDA PMID:8356051. Reason: Kdr triggers transient Ca2+ signals via PLCG1, captured by positive regulation of cytosolic calcium ion concentration; it is not a component of cellular calcium homeostasis. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96683 SOURCE WEAK OR INFERRED Donor paper not read here; Ca2+ signalling is a downstream output rather than homeostasis. Supporting Evidence: UniProtKB:O08775 Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate and the activation of protein kinase C |
| GO:0060562 epithelial tube morphogenesis | IEA GO_REF:0000117 | MODIFY | Summary: Epithelial tube morphogenesis inferred by ARBA. Reason: The tube morphogenesis Kdr drives is endothelial (GO:0061154, is_a epithelial tube morphogenesis), already annotated from rat aortic ring data. Proposed replacements: endothelial tube morphogenesis Supporting Evidence: PMID:25942475 TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation in vitro, as well as ex vivo vessel sprouting from rat aortic rings |
| GO:0061042 vascular wound healing | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Vascular wound healing (human IMP). Reason: Physiological context of VEGFR2-driven endothelial repair; non-core. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0061154 endothelial tube morphogenesis | IMP PMID:25942475 TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR... | KEEP AS NON CORE | Summary: Anti-VEGFR2 antibody TTAC-0001 blocks endothelial tube formation and sprouting of rat aortic rings. Reason: Supported by the full text; a facet of angiogenesis, kept non-core. Supporting Evidence: PMID:25942475 TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation in vitro, as well as ex vivo vessel sprouting from rat aortic rings |
| GO:0070161 anchoring junction | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Kdr localizes to endothelial cell-cell junctions with VE-cadherin/RAP1A. Reason: Supported but peripheral location. Supporting Evidence: UniProtKB:O08775 Localized with RAP1A at cell-cell junctions |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr signalling activates the MAPK/ERK1/2 cascade. Reason: Well-supported downstream output; non-core relative to receptor activity. Supporting Evidence: UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:0070482 response to oxygen levels | IEP PMID:15885787 Differential expression of vascular endothelial growth facto... | MARK AS OVER ANNOTATED | Summary: IEP from a pterygium/conjunctiva study of VEGF and VEGFR expression. Reason: The abstract describes human patient tissue and does not mention oxygen levels; expression in pterygia does not support a response to oxygen for rat Kdr. Full text not available, so the row is flagged rather than removed. Supporting Evidence: PMID:15885787 Tissue specimens from 75 patients treated for primary pterygia PMID:15885787 In addition to VEGF, VEGFR1 and VEGFR2 were detected in pterygia and conjunctivas |
| GO:0071526 semaphorin-plexin signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGFR2 participates with PlexinD1 in Sema3E signalling (mouse IGI PMID:25985275). Reason: Context-specific role; non-core. Supporting Evidence: UniProtKB:O08775 Modulates FLT1 and FLT4 signaling by forming heterodimers file:rat/Kdr/Kdr-deep-research-manual.md coreceptor activity and semaphorin-plexin signalling rest on an IGI with |
| GO:0071944 cell periphery | ISO GO_REF:0000121 | MODIFY | Summary: Cell periphery transferred from mouse Kdr. Reason: Cell periphery is entailed by plasma membrane; the specific supported location is GO:0005886, already annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96683 SUPPORTS TRANSFER Donor location is the plasma membrane/cell surface; cell periphery is the uninformative parent. Proposed replacements: plasma membrane Supporting Evidence: UniProtKB:O08775 Single-pass type I membrane protein UniProtKB:O08775 Detected on caveolae-enriched lipid rafts at the cell surface |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling drives endothelial cell migration and chemotaxis, including tip-cell migration in sprouting angiogenesis. Reason: Core cellular outcome of the receptor. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling drives endothelial cell migration and chemotaxis, including tip-cell migration in sprouting angiogenesis. Reason: Core cellular outcome of the receptor. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:0090141 positive regulation of mitochondrial fission | ISO GO_REF:0000121 | UNDECIDED | Summary: positive regulation of mitochondrial fission transferred from a human KDR row made by MGI as IGI (PMID:23798385, acts upstream). Reason: The donor genetic-interaction paper was not available; a mitochondrial/autophagy phenotype could reflect any of many downstream effects of VEGFR2 signalling and cannot be assessed here. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P35968 UNRESOLVED Donor IGI (PMID:23798385, assigned by MGI) not read. Supporting Evidence: UniProtKB:O08775 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD |
| GO:0097443 sorting endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: VEGF-bound Kdr is internalised and trafficked through endosomes, where it continues to signal before recycling or degradation. Reason: Endosomal trafficking is well documented for VEGFR2 and modulates signalling, but the core activity is at the plasma membrane. Supporting Evidence: UniProtKB:O08775 Is recycled from the plasma membrane to endosomes and back again |
| GO:0141150 positive regulation of nitric oxide-cGMP mediated signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kdr is required for VEGF-induced eNOS/NO production (human donors, acts upstream). Reason: Supported downstream output; non-core. Supporting Evidence: UniProtKB:O08775 Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells |
| GO:0141150 positive regulation of nitric oxide-cGMP mediated signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Kdr is required for VEGF-induced eNOS/NO production (human donors, acts upstream). Reason: Supported downstream output; non-core. Supporting Evidence: UniProtKB:O08775 Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells |
| GO:1901532 regulation of hematopoietic progenitor cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of hematopoietic progenitor differentiation (mouse IMP, acts upstream). Reason: Developmental consequence; non-core. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:1903010 regulation of bone development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of bone development from mouse Kdr mutant/inhibitor phenotypes (acts upstream of or within), reflecting endothelial-epithelial crosstalk during organogenesis. Reason: Developmental phenotype downstream of VEGF-Kdr vascular signalling; acceptable with the acts_upstream qualifier but not a core function. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:1904881 cellular response to hydrogen sulfide | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to hydrogen sulfide (human IDA PMID:26879375); H2S modifies an intracellular disulfide of VEGFR2. Reason: Supported by the UniProt activity-regulation note; non-core. Supporting Evidence: UniProtKB:O08775 May be regulated by hydrogen sulfide (H(2)S) levels via a sensitive intracellular disulfide bond |
| GO:2000352 negative regulation of endothelial cell apoptotic process | ISO GO_REF:0000121 | ACCEPT | Summary: Kdr signalling promotes endothelial cell survival. Reason: UniProt function statement; survival is a core outcome of VEGF-Kdr signalling via PI3K-AKT. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:2000352 negative regulation of endothelial cell apoptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: Kdr signalling promotes endothelial cell survival. Reason: UniProt function statement; survival is a core outcome of VEGF-Kdr signalling via PI3K-AKT. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells UniProtKB:O08775 Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway |
| GO:2001028 positive regulation of endothelial cell chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-Kdr signalling drives endothelial cell migration and chemotaxis, including tip-cell migration in sprouting angiogenesis. Reason: Core cellular outcome of the receptor. Supporting Evidence: UniProtKB:O08775 Promotes proliferation, survival, migration and differentiation of endothelial cells |
| GO:2001214 positive regulation of vasculogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of vasculogenesis by VEGF-Kdr signalling (mouse donors). Reason: Consistent with the vasculogenesis role; non-core restatement. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
| GO:2001214 positive regulation of vasculogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of vasculogenesis by VEGF-Kdr signalling (mouse donors). Reason: Consistent with the vasculogenesis role; non-core restatement. Supporting Evidence: UniProtKB:O08775 Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis |
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Download this section (compressed HTML)Q: GO:0070482 response to oxygen levels (rat Kdr IEP, PMID:15885787): the abstract describes human pterygium specimens and no oxygen manipulation. Is this row attached to the intended paper and species?
Q: GO:0050769 positive regulation of neurogenesis (PMID:15258583) is coded IEP, but the abstract reports a dominant-negative KDR experiment. Should the evidence be IMP?
Q: GO:0003416 endochondral bone growth (PMID:14612527): CP-547,632 inhibits FGFR as potently as VEGFR-2. Does the full text separate the two targets for the growth-plate phenotype?
Experiment: Endothelial-specific conditional deletion of Kdr in rat (or kinase-dead knock-in) to test which rat physiological phenotypes attributed to Kdr by pharmacology (hypotension, ocular neovascularization, growth-plate effects) depend on its kinase activity rather than on off-target inhibition of FGFRs or FLT1.
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