Vascular endothelial growth factor receptor 1 (VEGFR-1) is a receptor tyrosine kinase on endothelial cells that responds to VEGF-family growth factors, relaying signals that regulate the organization of the vasculature. It is not just a receptor though: the protein is also secreted as a soluble splice variant, sVEGFR-1, which is thought to act as an antagonist that sequesters ligands or forms non-signalling heterodimers with VEGFR-2. Angela Orecchia and co-workers reveal that sVEGFR-1 has an additional, quite different role: it moonlights as a ligand for integrins (see p. 3479). The authors show that cultured endothelial cells deposit sVEGFR-1 in the extracellular matrix (ECM) and that anchored sVEGFR-1 can stimulate endothelial cell adhesion, spreading and migration in various assays. They also demonstrate that antibodies against α5β1 integrin block these stimulatory effects, before going on to show that sVEGFR-1 can bind directly to the integrin in vitro. These findings indicate that VEGF-R1 has a novel function in angiogenesis that extends beyond that of a simple VEGF receptor. Indeed, given that α5β1 integrin is implicated in tumor-induced angiogenesis, sVEGFR-1's role as an ECM-associated integrin-binding protein could be particularly significant.
- © The Company of Biologists Limited 2003