Vascular Endothelial Growth Factor 165 (VEGF165)

VEGF165 is an angiogenic cytokine that also regulates vascular permeability.The neuropilin-1 (np1) receptor binds the 165 amino-acid form of  VEGF165 and functions as an enhancer that potentiates VEGF165 signaling via the VEGFR-2 tyrosine-kinase receptor. A VEGF165 mutant (VEGF165KF) that binds to neuropilins but displays a much lower affinity toward VEGFR-1 and VEGFR-2. VEGF165KF failed to induce VEGFR-2 phosphorylation in cells lacking neuropilins. However, in the presence of np1, VEGF165KF bound weakly to VEGFR-2, induced VEGFR-2 phosphorylation, and activated ERK1/2. Interestingly, VEGF165KF did not promote formation of VEGFR-2/np1 complexes nor did high concentrations of VEGF165KF inhibit VEGF165 induced formation of such complexes, suggesting that VEGF165 does not stabilize VEGFR-2/np1 complexes by forming bridges spanning VEGFR-2 and np1.