Canonical and noncanonical vascular endothelial growth factor pathways: New developments in biology and signal transduction

Courtney K. Domigan, Safiyyah Ziyad, M. Luisa Iruela-Arispe*

*Corresponding author for this work

Research output: Contribution to journalReview article

35 Scopus citations

Abstract

The past 5 years have witnessed a significant expansion in our understanding of vascular endothelial growth factor (VEGF) signaling. In particular, the process of canonical activation of VEGF receptor tyrosine kinases by homodimeric VEGF molecules has now been broadened by the realization that heterodimeric ligands and receptors are also active participants in the signaling process. Although heterodimer receptors were described 2 decades ago, their impact, along with the effect of additional cell surface partners and novel autocrine VEGF signaling pathways, are only now starting to be clarified. Furthermore, ligand-independent signaling (noncanonical) has been identified through galectin and gremlin binding and upon rise of intracellular levels of reactive oxygen species. Activation of the VEGF receptors in the absence of ligand holds immediate implications for therapeutic approaches that exclusively target VEGF. The present review provides a concise summary of the recent developments in both canonical and noncanonical VEGF signaling and places these findings in perspective to their potential clinical and biological ramifications.

Original languageEnglish (US)
Pages (from-to)30-39
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume35
Issue number1
DOIs
StatePublished - Jan 3 2015

Keywords

  • Endothelial Cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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