| Autor: |
Smith, GA, Fearnley, GW, Zani, IA, Wheatcroft, SB, Tomlinson, DC, Harrison, MA, Ponnambalam, S |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| ISSN: |
1398-9219 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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