Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration

Blood. 2006 Aug 15;108(4):1243-50. doi: 10.1182/blood-2005-11-4447. Epub 2006 Apr 18.

Abstract

Neuropilin 2 (NRP2) is a receptor for the vascular endothelial growth factor (VEGF) and the semaphorin (SEMA) families, 2 unrelated ligand families involved in angiogenesis and neuronal guidance. NRP2 specifically binds VEGF-A and VEGF-C, although the biological relevance of these interactions in human endothelial cells is poorly understood. In this study, we show that both VEGF-A and VEGF-C induce the interaction of NRP2 with VEGFR-2. This interaction correlated with an enhancement of the VEGFR-2 phosphorylation threshold. Overexpression of NRP2 in primary human endothelial cells promoted cell survival induced by VEGF-A and VEGF-C. In contrast, SEMA3F, another ligand for NRP2, was able to inhibit human endothelial cell survival and migration induced by VEGF-A and VEGF-C. Moreover, a siRNA targeting specifically NRP2 was a potent inhibitor of human endothelial cell migration induced by VEGF-A and VEGF-C. Thus, our data indicate that NRP2 acts as a coreceptor that enhances human endothelial cell biological responses induced by VEGF-A and VEGF-C.

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Endothelial Cells / physiology*
  • Gene Expression
  • Humans
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / pharmacology
  • Neuropilin-2 / antagonists & inhibitors
  • Neuropilin-2 / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • RNA, Small Interfering / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor C / metabolism
  • Vascular Endothelial Growth Factor C / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism*

Substances

  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropilin-2
  • RNA, Small Interfering
  • SEMA3F protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3