Vascular Endothelial Growth Factor 121 (VEGF121)

is a VEGF form that does not bind to neuropilins. Surprisingly, both np1 and neuropilin-2 (np2) enhanced VEGF₁₂₁-induced phosphorylation of VEGFR-2 and VEGF₁₂₁-induced proliferation of endothelial cells. The enhancement of VEGF₁₂₁ activity by np1 was accompanied by a 10-fold increase in binding affinity to VEGFR-2 and was not associated with the formation of new VEGFR-2/np1 complexes. These observations suggest that neuropilins enhance the activity of VEGF forms that do not bind to neuropilins, indicate that np2 is a functional VEGF receptor, and imply that spontaneously formed VEGFR-2/np1 complexes suffice for efficient neuropilin mediated enhancement of VEGF activity.—Shraga-Heled, N., Kessler, O., Prahst, C., Kroll, J., Augustin, H., Neufeld, G. Neuropilin-1 and neuropilin-2 enhance VEGF₁₂₁ stimulated signal transduction by the VEGFR-2 receptor.