Signaling by VEGF

Stable Identifier
R-HSA-194138
Type
Pathway
Species
Homo sapiens
Synonyms
Signaling by Vascular Epithelial Growth Factors (VEGF)
Locations in the PathwayBrowser
Summation

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 (Hicklin and Ellis, 2005; Shibuya and Claesson-Welsh, 2006).
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.

Literature References
PubMed ID Title Journal Year
15585754 Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis

Hicklin, DJ, Ellis, LM

J Clin Oncol 2005
16336962 Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis

Shibuya, M, Claesson-Welsh, L

Exp Cell Res 2006
16835467 Signal transduction via vascular endothelial growth factor (VEGF) receptors and their roles in atherogenesis

Matsumoto, T, Mugishima, H

J Atheroscler Thromb 2006
13678960 VEGF-receptor signal transduction

Cross, MJ, Dixelius, J, Matsumoto, T, Claesson-Welsh, L

Trends Biochem Sci 2003
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