R-Ras protein inhibits autophosphorylation of vascular endothelial growth factor receptor 2 in endothelial cells and suppresses receptor activation in tumor vasculature

Background: Excessive stimulation of endothelial cells by VEGF is a major cause of aberrant angiogenesis and leaky blood vessels in various medical conditions. Results: The Small GTPase R-Ras inhibits VEGF-induced internalization and tyrosine phosphorylation of VEGF receptor 2. Conclusion: R-Ras suppresses chronic and acute endothelial cell stimulation by VEGF. Significance: Our study identifies a mechanism of attenuating VEGF signaling by a Ras homolog and offers mechanistic insights into the regulation of angiogenesis by this small GTPase.