Signal relays in the VEGF system

Front Biosci. 1999 Feb 1;4:D141-52. doi: 10.2741/A417.

Abstract

A considerable progress has been made during the past years in elucidating the molecular actors of angiogenesis. Vascular endothelial growth factor turned out to represent the major inducer of angiogenesis. Optional splicing of its pre messenger RNA generates various isoforms which differ not only by their storage in the extracellular matrix but also by their signaling pathways. VEGF binds and activates two tyrosine kinase receptors called VEGFR1 and VEGFR2 and neuropilin-1. The elucidation of the transduction pathways of each receptor suggests that VEGFR1 mediates cell migration whereas VEGFR2 mediates cell proliferation. The construction of internal images of VEGF by the anti-idiotypic antibody strategy allowed us to determine that quiescent endothelial cells need to be activated by so far unknown factors to become competent to respond to mitogenic signals and acquire an angiogenic phenotype. The discovery of the mechanisms of action of the VEGF system has allowed the design of promising drugs which already entered the pre-clinical or clinical assays.

Publication types

  • Review

MeSH terms

  • Animals
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / physiology*
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental
  • Humans
  • Lymphokines / genetics
  • Lymphokines / metabolism
  • Lymphokines / physiology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology*
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Growth Factor / chemistry
  • Receptors, Growth Factor / metabolism
  • Receptors, Growth Factor / physiology*
  • Receptors, Vascular Endothelial Growth Factor
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor