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Complex formation between VEGFR2 and the ?2-adrenoceptor

Kilpatrick, Laura E.; Alcobia, Diana C.; White, Carl W.; Peach, Chloe J.; Glenn, Jackie R.; Zimmerman, Kris; Kondrashov, Alexander; Pfleger, Kevin D.G.; Friedman Ohana, Rachel; Robers, Matthew B.; Wood, Keith V.; Sloan, Erica K.; Woolard, Jeanette; Hill, Stephen J.


Diana C. Alcobia

Carl W. White

Chloe J. Peach

Jackie R. Glenn

Kris Zimmerman

Kevin D.G. Pfleger

Rachel Friedman Ohana

Matthew B. Robers

Keith V. Wood

Erica K. Sloan

Professor of Cardiovascular Physiology and Pharmacology

Professor of Molecular Pharmacology


Vascular endothelial growth factor (VEGF) is an important mediator of endothelial cell proliferation and angiogenesis via its receptor VEGFR2. A common tumor associated with elevated VEGFR2 signaling is infantile hemangioma that is caused by a rapid proliferation of vascular endothelial cells. The current first-line treatment for infantile hemangioma is the ?-adrenoceptor antagonist, propranolol, although its mechanism of action is not understood. Here we have used bioluminescence resonance energy transfer and VEGFR2 genetically tagged with NanoLuc luciferase to demonstrate that oligomeric complexes involving VEGFR2 and the ?2-adrenoceptor can be generated in both cell membranes and intracellular endosomes. These complexes are induced by agonist treatment and retain their ability to couple to intracellular signaling proteins. Furthermore, coupling of ?2-adrenoceptor to ?-arrestin2 is prolonged by VEGFR2 activation. These data suggest that protein-protein interactions between VEGFR2, the ?2-adrenoceptor, and ?-arrestin2 may provide insight into their roles in health and disease.


Kilpatrick, L. E., Alcobia, D. C., White, C. W., Peach, C. J., Glenn, J. R., Zimmerman, K., …Hill, S. J. (2019). Complex formation between VEGFR2 and the β2-adrenoceptor. Cell Chemical Biology, 26(6), 830-841.e9.

Journal Article Type Article
Acceptance Date Feb 24, 2019
Online Publication Date Apr 4, 2019
Publication Date Jun 20, 2019
Deposit Date Mar 4, 2019
Publicly Available Date Apr 5, 2020
Journal Cell Chemical Biology
Electronic ISSN 2451-9448
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 26
Issue 6
Pages 830-841.e9
Keywords VEGFR2; ?2-adrenoceptors; Ligand binding; BRET; NanoBRET; Receptor oligomerization; ?-arrestin; CRISPR/Cas9
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