Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells

Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11709-14. doi: 10.1073/pnas.95.20.11709.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Baculoviridae / genetics
  • Base Sequence
  • Binding Sites / genetics
  • Cattle
  • Cells, Cultured
  • Cysteine / genetics
  • DNA Primers / genetics
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Mice
  • Mutagenesis, Site-Directed
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activators / metabolism*
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spodoptera
  • Transfection
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Vascular Endothelial Growth Factor B
  • Vascular Endothelial Growth Factor Receptor-1


  • DNA Primers
  • Endothelial Growth Factors
  • Plasminogen Activator Inhibitor 1
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor B
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-1
  • Plasminogen Activators
  • Urokinase-Type Plasminogen Activator
  • Cysteine