Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor

Cell. 1998 Mar 20;92(6):735-45. doi: 10.1016/s0092-8674(00)81402-6.

Abstract

Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, binds to two receptor tyrosine kinases, KDR/Flk-1 and Flt-1. We now describe the purification and the expression cloning from tumor cells of a third VEGF receptor, one that binds VEGF165 but not VEGF121. This isoform-specific VEGF receptor (VEGF165R) is identical to human neuropilin-1, a receptor for the collapsin/semaphorin family that mediates neuronal cell guidance. When coexpressed in cells with KDR, neuropilin-1 enhances the binding of VEGF165 to KDR and VEGF165-mediated chemotaxis. Conversely, inhibition of VEGF165 binding to neuropilin-1 inhibits its binding to KDR and its mitogenic activity for endothelial cells. We propose that neuropilin-1 is a novel VEGF receptor that modulates VEGF binding to KDR and subsequent bioactivity and therefore may regulate VEGF-induced angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Cell Line / chemistry
  • Cell Line / cytology
  • Cell Line / metabolism
  • Chemotaxis / physiology
  • Cloning, Molecular
  • Endothelial Growth Factors / chemistry
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / chemistry*
  • Endothelium, Vascular / cytology
  • Exons / physiology
  • Gene Expression
  • Humans
  • Isomerism
  • Lymphokines / chemistry
  • Lymphokines / metabolism*
  • Molecular Sequence Data
  • Neovascularization, Physiologic / physiology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Neuropilin-1
  • RNA, Messenger / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / isolation & purification
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / isolation & purification
  • Receptors, Growth Factor / metabolism
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / isolation & purification
  • Receptors, Mitogen / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Umbilical Cord / cytology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antigens, Surface
  • Endothelial Growth Factors
  • Lymphokines
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Growth Factor
  • Receptors, Mitogen
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Neuropilin-1
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor

Associated data

  • GENBANK/AF016050
  • GENBANK/AF016098