VEGF Receptor Signaling

Vascular endothelial growth factor (VEGF) stimulates mitogenesis of endothelial cells and increases vessel permeability. VEGF exerts its effects by binding to one of its three receptors (VEGFR-1/Flt-1, VEGFR-2/KDR/Flk-1, VEGFR-3/Flt-4). Upon binding of the ligand the receptor under goes transautophosphorylation and subsequent activation of a cell type-dependent signaling cascade. Signaling cascades that have been implicated in VEGF action include Src, PLC-g, MAPK, as well as STAT3 and STAT5. VEGF initiates embryonic vasculogenesis and triggers angiogenic sprouting via its activation of VEGFR-2 on vascular endothelial cells. VEGF activation of VEGFR-1 may limit cell proliferation induced by activation of VEGFR-2 and, thus, may limit VEGF-induced angiogenesis.

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References:

Yancopoulos, G.D., et al., Vascular-specific growth factors and blood vessel formation. Nature, 407, 242-248 (2000).

Clauss, M., Molecular biology of the VEGF and the VEGF receptor family. Semin. Thromb. Hemost., 26, 561-569 (2000).

Neufeld, G., et al., Vascular endothelial growth factor (VEGF) and its receptors. FASEB J., 13, 9-22 (1999).