Vascular Endothelial Growth Factor (VEGF) family members are potent mitogenic and angiogenic proteins with critical physiological roles in development and wound healing. In addition, they are also centrally involved in promoting tumor growth and vascular disease. Members of the VEGF gene family include VEGF/VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and Placental Growth Factor (PlGF). Alternative splicing of VEGF, VEGF-B, and PlGF can generate multiple isoforms with different biological properties. These isoforms include VEGF110
, PlGF-1, PlGF-2, PlGF-3, and PlGF-4. VEGFs homodimerize and transduce intracellular signals by binding to VEGF receptors (VEGF R1, VEGF R2, and VEGF R3) and Neuropilins, which are localized to the cell surface and have a unique specificity for different VEGF isoforms. Ligand binding promotes receptor dimerization, autophosphorylation, and activation of multiple downstream signaling cascades that stimulate vascular permeability, cell survival, proliferation, migration, or adhesion.