Mechanisms and regulation of endothelial VEGF receptor signalling

Nat Rev Mol Cell Biol. 2016 Oct;17(10):611-25. doi: 10.1038/nrm.2016.87. Epub 2016 Jul 27.


Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are uniquely required to balance the formation of new blood vessels with the maintenance and remodelling of existing ones, during development and in adult tissues. Recent advances have greatly expanded our understanding of the tight and multi-level regulation of VEGFR2 signalling, which is the primary focus of this Review. Important insights have been gained into the regulatory roles of VEGFR-interacting proteins (such as neuropilins, proteoglycans, integrins and protein tyrosine phosphatases); the dynamics of VEGFR2 endocytosis, trafficking and signalling; and the crosstalk between VEGF-induced signalling and other endothelial signalling cascades. A clear understanding of this multifaceted signalling web is key to successful therapeutic suppression or stimulation of vascular growth.

Publication types

  • Review

MeSH terms

  • Animals
  • Endocytosis
  • Humans
  • Neovascularization, Physiologic
  • Protein Transport
  • Receptor Cross-Talk
  • Signal Transduction*
  • Vascular Endothelial Growth Factor Receptor-2 / physiology*
  • Vascular Endothelial Growth Factors / physiology*


  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor Receptor-2