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.

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.

Mesh Terms:
Animals, Binding Sites, COS Cells, Endothelial Growth Factors, Nerve Tissue Proteins, Neuropilin-1, Protein Binding, Protein Isoforms, RNA Splicing, Receptors, Cell Surface, Signal Transduction, Vascular Endothelial Growth Factor B

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