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Complex Formation between VEGFR2 and the β2-Adrenoceptor.
Laura E Kilpatrick1, Diana C Alcobia2, Carl W White3
1Division of Physiology, Pharmacology & Neuroscience, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK; Centre of Membrane Proteins and Receptors, University of Birmingham and University of Nottingham, The Midlands, UK.
Cell Chemical Biology
|April 9, 2019
Summary
Vascular endothelial growth factor receptor 2 (VEGFR2) and beta-2 adrenoceptors form complexes that influence signaling. This interaction may explain how propranolol treats infantile hemangioma.
Area of Science:
- Molecular biology
- Cellular signaling
- Pharmacology
Background:
- Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 are key in angiogenesis.
- Infantile hemangioma involves excessive vascular endothelial cell proliferation.
- Propranolol is the primary treatment for infantile hemangioma, but its mechanism is unclear.
Purpose of the Study:
- To investigate the molecular interactions between VEGFR2 and the beta-2 adrenoceptor.
- To elucidate the mechanism of propranolol's action in infantile hemangioma.
Main Methods:
- Bioluminescence resonance energy transfer (BRET) was used.
- VEGFR2 was genetically tagged with NanoLuc luciferase.
Main Results:
- Oligomeric complexes of VEGFR2 and beta-2 adrenoceptor formed in cell membranes and endosomes.
- These complexes were induced by agonist treatment and coupled to signaling proteins.
- VEGFR2 activation prolonged beta-2 adrenoceptor-beta-arrestin2 coupling.
Conclusions:
- Protein-protein interactions between VEGFR2, beta-2 adrenoceptor, and beta-arrestin2 are identified.
- These interactions offer insights into infantile hemangioma pathogenesis and propranolol's therapeutic effects.
Keywords:
BRETCRISPR/Cas9NanoBRETVEGFR2infantile haemangiomareceptor oligomerisationβ(2)-adrenoceptorsβ-arrestinMore Related Videos
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