Angiogenesis Regulators

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 undergoes trans-autophosphorylation and subsequent activation of a cell type-dependent signaling cascade. Signaling cascades that have been implicated in VEGF action include Src, PLC-γ, 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.
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).

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