| First Author | Robinson SD | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 49 | Pages | 33966-81 |
| PubMed ID | 19837659 | Mgi Jnum | J:157796 |
| Mgi Id | MGI:4436979 | Doi | 10.1074/jbc.M109.030700 |
| Citation | Robinson SD, et al. (2009) Alphav beta3 integrin limits the contribution of neuropilin-1 to vascular endothelial growth factor-induced angiogenesis. J Biol Chem 284(49):33966-81 |
| abstractText | Both vascular endothelial growth factor receptors (VEGFR) and integrins are major regulators of VEGF-induced angiogenesis. Previous work has shown that beta3 integrin can regulate negatively VEGFR2 expression. Here we show that beta3 integrin can regulate negatively VEGF-mediated angiogenesis by limiting the interaction of the co-receptor NRP1 (neuropilin-1) with VEGFR2. In the presence of alphav beta3 integrin, NRP1 contributed minimally to VEGF-induced angiogenic processes in vivo, ex vivo, and in vitro. Conversely, when beta3 integrin expression is absent or low or its function is blocked with RGD-mimetic inhibitors, VEGF-mediated responses became NRP1-dependent. Indeed, combined inhibition of beta3 integrin and NRP1 decreased VEGF-mediated angiogenic responses further than individual inhibition of these receptors. We also show that alphav beta3 integrin can associate with NRP1 in a VEGF-dependent fashion. Our data suggest that beta3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2. |
