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Updated: Jul 29, 2025
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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
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The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function
William R Critchley1, Gina A Smith1, Ian C Zachary2
1Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
Journal of Cell Science
|May 25, 2023
Summary
UBE2D1 and UBE2D2 enzymes regulate vascular endothelial growth factor receptor 2 (VEGFR2) ubiquitination and proteolysis. Their depletion increases VEGFR2 levels, enhancing angiogenesis and VEGF-A signaling in endothelial cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Vascular endothelial growth factor receptor 2 (VEGFR2) is crucial for endothelial cell function and angiogenesis.
- VEGFR2 ubiquitination regulates its trafficking and degradation, but involved enzymes are not fully identified.
Purpose of the Study:
- To identify ubiquitin-conjugating enzymes (E2) that regulate VEGFR2 ubiquitination and proteolysis.
- To investigate the functional consequences of altered VEGFR2 ubiquitination on endothelial cells.
Main Methods:
- Reverse genetics screen of human E2 ubiquitin-conjugating enzymes.
- Endothelial cell culture and manipulation (depletion of UBE2D1/UBE2D2).
- Analysis of VEGFR2 levels, signaling pathways (MAPK, PLCγ1, Akt), and endothelial tubulogenesis.
Main Results:
- Depletion of UBE2D1 or UBE2D2 increased steady-state and plasma membrane VEGFR2 levels.
- Increased VEGFR2 levels enhanced VEGF-A-stimulated canonical signaling pathways.
- Reduced UBE2D levels promoted VEGFR2 recycling and stimulated endothelial tubulogenesis.
Conclusions:
- UBE2D1 and UBE2D2 play a key role in VEGFR2 ubiquitination and proteolysis.
- These enzymes regulate VEGFR2 trafficking, signaling, and function in angiogenesis.
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