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	J. Biol. Chem. Jul (1999); 274(30):21217-22
Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1.
Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K
Molecular/Cancer Biology Laboratory, Haartman Institute, University of Helsinki, FIN-00014 Helsinki, Finland.
Abstract: Vascular endothelial growth factor B (VEGF-B) is expressed in various tissues, especially strongly in the heart, and binds selectively to one of the VEGF receptors, VEGFR-1. The two splice isoforms, VEGF-B(167) and VEGF-B(186), have identical NH(2)-terminal cystine knot growth factor domains but differ in their COOH-terminal domains which give these forms their distinct biochemical properties. In this study, we show that both splice isoforms of VEGF-B bind specifically to Neuropilin-1 (NRP1), a receptor for collapsins/semaphorins and for the VEGF(165) isoform. The NRP1 binding of VEGF-B could be competed by an excess of VEGF(165). The binding of VEGF-B(167) was mediated by the heparin binding domain, whereas the binding of VEGF-B(186) to NRP1 was regulated by exposure of a short COOH-terminal proline-rich peptide upon its proteolytic processing. In immunohistochemistry, NRP1 distribution was found to be overlapping or adjacent to known sites of VEGF-B expression in several tissues, in particular in the developing heart, suggesting the involvement of VEGF-B in NRP1-mediated signaling.
[PUBMED: 10409677]