Pathway
Signaling by VEGF
In normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angiogenesis). In tumor progression, activation of VEGF pathways promotes tumor vascularization, facilitating tumor growth and metastasis. Abnormal VEGF function is also associated with inflammatory diseases including atherosclerosis, and hyperthyroidism. The members of the VEGF and VEGF-receptor protein families have distinct but overlapping ligand-receptor specificities, cell-type expression, and function. VEGF-receptor activation in turn regulates a network of signaling processes in the body that promote endothelial cell growth, migration and survival.
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Molecular features of the VGF signaling cascades are outlined in the figure below (from Olsson et al. 2006; Nature Publishing Group). Tyrosine residues in the intracellular domains of VEGF receptors 1, 2,and 3 are indicated by dark blue boxes; residues susceptible to phosphorylation are numbered. A circled R indicates that phosphorylation is regulated by cell state (VEGFR2), by ligand binding (VEGFR1), or by heterodimerization (VEGFR3). Specific phosphorylation sites (boxed numbers) bind signaling molecules (dark blue ovals), whose interaction with other cytosolic signaling molecules (light blue ovals) leads to specific cellular (pale blue boxes) and tissue-level (pink boxes) responses in vivo. Signaling cascades whose molecular details are unclear are indicated by dashed arrows. DAG, diacylglycerol; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; FAK, focal adhesion kinase; HPC, hematopoietic progenitor cell; HSP27, heat-shock protein-27; MAPK, mitogen-activated protein kinase; MEK, MAPK and ERK kinase; PI3K, phosphatidylinositol 3' kinase; PKC, protein kinase C; PLCgamma, phospholipase C-gamma; Shb, SH2 and beta-cells; TSAd, T-cell-specific adaptor.
In the current release, the first events in these cascades - the interactions between VEGF proteins and their receptors - are annotated.
What the reference databases state
Statements
104 statements
104 statements · 1 reference database · Subject: Signaling by VEGF · Sources: Reactome
- AAMP participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ABI1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ABI2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ACTB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ACTG1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- AHCYL1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- AKT1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- AKT2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- AKT3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- AXL participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- BAIAP2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- BCAR1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
Show the remaining 92
- BRK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CALM1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CAV1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CDC42 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CDH5 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CRK participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CTNNA1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CTNNB1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CTNND1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CYBA participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CYBB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CYFIP1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- CYFIP2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- DOCK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ELMO1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ELMO2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- FLT1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- FLT4 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- FYN participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- HRAS participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- HSP90AA1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- HSPB1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ITGAV participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ITGB3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ITPR1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ITPR2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ITPR3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- JUP participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- KDR participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPK11 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPK12 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPK13 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPK14 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPKAP1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPKAPK2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MAPKAPK3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MLST8 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- MTOR participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCF1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCF2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCF4 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCK2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCKAP1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NCKAP1L participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NOS3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NRAS participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NRP1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- NRP2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PAK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PAK2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PAK3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PDPK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PGF participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PIK3CA participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PIK3CB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PIK3R1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PIK3R2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PLCG1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKACA participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKACB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKACG participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKCA participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKCB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKCD participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRKCZ participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PRR5 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PTK2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PTK2B participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- PXN participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- RAC1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- RASA1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- RHOA participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- RICTOR participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ROCK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- ROCK2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- SH2D2A participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- SHB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- SHC2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- SPHK1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- THEM4 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- TRIB3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VAV1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VAV2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VAV3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VEGFA participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VEGFB participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VEGFC participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- VEGFD participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- WASF1 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- WASF2 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only
- WASF3 participates in Signaling by VEGFProteinReactome R-HSA-194138Inferred only