Gina A. Smith, Gareth W. Fearnley, Izma Abdul‐Zani, Stephen B. Wheatcroft, Darren C. Tomlinson, Michael A. Harrison, Sreenivasan Ponnambalam
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.
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 April 2017.
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#14,256,844
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Outputs from Traffic
#703
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Outputs of similar age
#190,669
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Outputs of similar age from Traffic
#7
of 19 outputs
Altmetric has tracked 24,542,484 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,255 research outputs from this source. They receive a mean Attention Score of 3.7. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
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We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
