VEGFA is the prototype member of a family of proteins that includes VEGFB, VEGFC, VEGFD, VEGFE (a virally encoded protein) and placental growth factor (PlGF also known as PGF). These proteins, which are structurally related to the platelet-derived growth factor (PDGF) family of proteins have a range of tissue distributions and functions VEGFA gene, isoforms and encoded proteins. Proteolysis plays an important part in regulating the biological activity of VEGFA proteins. The interactions of VEGFA family members with different VEGFRs are outlined in figure.
Of the two RTKs, VEGFR2 is the main mediator of the roles of VEGFA in cell proliferation, angiogenesis and vessel permeabilization. Binding of VEGFA to VEGFR2 on endothelial cells leads to receptor dimerization and autophosphorylation, Regulation of VEGFA gene expression. The expression of VEGFA is primarily stimulated by hypoxia, mediated by the hypoxia-inducible factor (HIF), which also triggers the expression of other hypoxiaregulated genes. VEGFA expression is also regulated by other factors, such as epidermal growth factor (EGF) and PDGF9, and by oncogenic mutations.