%0 Journal Article %J Proc Natl Acad Sci U S A %D 1998 %T Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells %A Olofsson, B %A Korpelainen, E %A Pepper, M S %A Mandriota, S J %A Aase, K %A Kumar, V %A Gunji, Y %A Jeltsch, M M %A Shibuya, M %A Alitalo, K %A Eriksson, U %X The vascular endothelial growth factor (VEGF) family has recently expanded by the identification and cloning of three additional members, namely VEGF-B, VEGF-C, and VEGF-D. In this study we demonstrate that VEGF-B binds selectively to VEGF receptor-1/Flt-1. This binding can be blocked by excess VEGF, indicating that the interaction sites on the receptor are at least partially overlapping. Mutating the putative VEGF receptor-1/Flt-1 binding determinants Asp63, Asp64, and Glu67 to alanine residues in VEGF-B reduced the affinity to VEGF receptor-1 but did not abolish binding. Mutational analysis of conserved cysteines contributing to VEGF-B dimer formation suggest a structural conservation with VEGF and platelet-derived growth factor. Proteolytic processing of the 60-kDa VEGF-B186 dimer results in a 34-kDa dimer containing the receptor-binding epitopes. The binding of VEGF-B to its receptor on endothelial cells leads to increased expression and activity of urokinase type plasminogen activator and plasminogen activator inhibitor 1, suggesting a role for VEGF-B in the regulation of extracellular matrix degradation, cell adhesion, and migration. %B Proc Natl Acad Sci U S A %V 95 %P 11709 - 14 %8 1998/Sep/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/9751730 %N 20 %! Proceedings of the National Academy of Sciences of the United States of America