avβ3 Integrin Limits the Contribution of Neuropilin-1 to Vascular Endothelial Growth Factor-induced Angiogenesis

Robinson, Stephen D., Reynolds, Louise E., Kostourou, Vassiliki, Reynolds, Andrew R., da Silva, Rita Graça, Tavora, Bernardo, Baker, Marianne, Marshall, John F. and Hodivala-Dilke, Kairbaan M. (2009) avβ3 Integrin Limits the Contribution of Neuropilin-1 to Vascular Endothelial Growth Factor-induced Angiogenesis. Journal of Biological Chemistry, 284 (49). pp. 33966-33981. ISSN 0021-9258

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Abstract

Both vascular endothelial growth factor receptors (VEGFR) and integrins are major regulators of VEGF-induced angiogenesis. Previous work has shown that ß3 integrin can regulate negatively VEGFR2 expression. Here we show that ß3 integrin can regulate negatively VEGF-mediated angiogenesis by limiting the interaction of the co-receptor NRP1 (neuropilin-1) with VEGFR2. In the presence of avß3 integrin, NRP1 contributed minimally to VEGF-induced angiogenic processes in vivo, ex vivo, and in vitro. Conversely, when ß3 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 ß3 integrin and NRP1 decreased VEGF-mediated angiogenic responses further than individual inhibition of these receptors. We also show that avß3 integrin can associate with NRP1 in a VEGF-dependent fashion. Our data suggest that ß3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Users 2731 not found.
Date Deposited: 22 Nov 2011 14:02
Last Modified: 11 Nov 2019 17:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/35535
DOI: 10.1074/jbc.M109.030700

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