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First published online July 31, 2003

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VEGFR-1: receptor, antagonist, integrin ligand!

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 5ß1 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 5ß1 integrin is implicated in tumor-induced angiogenesis, sVEGFR-1's role as an ECM-associated integrin-binding protein could be particularly significant.

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Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the 5ß1 integrin

Angela Orecchia, Pedro Miguel Lacal, Cataldo Schietroma, Veronica Morea, Giovanna Zambruno, and Cristina Maria Failla
JCS 2003 116: 3479-3489. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?