Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]

J Biol Chem. 2000 Jun 16;275(24):18040-5. doi: 10.1074/jbc.M909259199.

Abstract

Neuropilin-1 (np-1) and neuropilin-2 (np-2) are receptors for axon guidance factors belonging to the class 3 semaphorins. np-1 also binds to the 165-amino acid heparin-binding form of VEGF (VEGF(165)) but not to the shorter VEGF(121) form, which lacks a heparin binding ability. We report that human umbilical vein-derived endothelial cells express the a17 and a22 splice forms of the np-2 receptor. Both np-2 forms bind VEGF(165) with high affinity in the presence of heparin (K(D) 1.3 x 10(-10) m) but not VEGF(121). np-2 also binds the heparin-binding form of placenta growth factor. These binding characteristics resemble those of np-1. VEGF(145) is a secreted heparin binding VEGF form that contains the peptide encoded by exon 6 of VEGF but not the peptide encoded by exon 7, which is present in VEGF(165). VEGF(145) binds to np-2 with high affinity (K(D) 7 x 10(-10) m). Surprisingly, VEGF(145) did not bind to np-1. Indeed, VEGF(145) does not bind to MDA-MB-231 breast cancer cells, which predominantly express np-1. By contrast, VEGF(145) binds to human umbilical vein-derived endothelial cells, which express both np-1 and np-2. The binding of VEGF(165) to porcine aortic endothelial cells expressing recombinant np-2 did not affect the proliferation or migration of the cells. Nevertheless, it is possible that VEGF-induced np-2-mediated signaling will take place only in the presence of other VEGF receptors such as VEGF receptor-1 or VEGF receptor-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae
  • Breast Neoplasms / metabolism
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Endothelial Growth Factors / metabolism*
  • Endothelium / metabolism
  • Female
  • Growth Substances / metabolism*
  • Humans
  • Lymphokines / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Neuropilin-1
  • Placenta
  • Placenta Growth Factor
  • Pregnancy Proteins / metabolism*
  • Protein Binding
  • Protein Isoforms / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Spodoptera
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Growth Substances
  • Lymphokines
  • Nerve Tissue Proteins
  • PGF protein, human
  • Pregnancy Proteins
  • Protein Isoforms
  • Receptors, Cell Surface
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Placenta Growth Factor
  • Neuropilin-1