VEGFR2 trafficking, signaling and proteolysis is regulated by the ubiquitin isopeptidase USP8
Gina A. Smith, Gareth W. Fearnley, Izma A. Zani, Stephen B. Wheatcroft, Darren C. Tomlinson, Michael A. Harrison and Sreenivasan Ponnambalam
Accepted manuscript online: 13 OCT 2015 02:17AM EST | DOI: 10.1111/tra.12341
Endothelial cells regulate many aspects of vascular physiology including blood pressure, vascular repair and new blood vessel sprouting. Binding of vascular endothelial growth factor A (VEGF-A) to a receptor tyrosine kinase (VEGFR2) stimulates intracellular signaling and the endothelial response. We show that the ubiquitin isopeptidase, USP8, is essential for VEGFR2 trafficking, de-ubiquitination, signal transduction and proteolysis. Biochemical pathways that control the ubiquitination and de-ubiquitination of VEGFR2 thus regulate endothelial decision-making processes that influence vascular physiology.