Smith, GA, Fearnley, GW, Zani, IA et al. (4 more authors) (2016) VEGFR2 trafficking, signaling and proteolysis is regulated by the ubiquitin isopeptidase USP8. Traffic, 17 (1). pp. 53-65. ISSN 1398-9219
Abstract
Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular function. VEGF-A binding to vascular endothelial growth factor receptor 2 (VEGFR2) stimulates endothelial signal transduction and regulates multiple cellular responses. Activated VEGFR2 undergoes ubiquitination but the enzymes that regulate this post-translational modification are unclear. In this study, the de-ubiquitinating enzyme, USP8, is shown to regulate VEGFR2 trafficking, de-ubiquitination, proteolysis and signal transduction. USP8-depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system. In addition, perturbed VEGFR2 trafficking impaired VEGF-A-stimulated signal transduction in USP8-depleted cells. Thus, regulation of VEGFR2 ubiquitination and de-ubiquitination has important consequences for the endothelial cell response and vascular physiology.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Traffic published by John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | VEGF-A; VEGFR2; trafficking; USP8; de-ubiquitination; signal transduction; proteolysis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cardiovascular Science (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation FS/12/20/29462 |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Oct 2015 10:38 |
Last Modified: | 28 Aug 2020 11:04 |
Published Version: | http://dx.doi.org/10.1111/tra.12341 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/tra.12341 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:90882 |