Complex Formation between VEGFR2 and the β2-Adrenoceptor

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 β-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 β2-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 β2-adrenoceptor to β-arrestin2 is prolonged by VEGFR2 activation. These data suggest that protein-protein interactions between VEGFR2, the β2-adrenoceptor, and β-arrestin2 may provide insight into their roles in health and disease. Kilpatrick et al. have used bioluminescence resonance energy transfer (BRET) and VEGFR2 tagged with NanoLuc luciferase, to demonstrate that oligomeric complexes involving VEGFR2 and β2-adrenoceptors can be generated in both cell membranes and intracellular endosomes. These complexes are agonist sensitive and retain their ability to couple to intracellular signaling proteins.

Original languageEnglish
Pages (from-to)830-841.e9
Number of pages21
JournalCell Chemical Biology
Volume26
Issue number6
DOIs
Publication statusPublished - 20 Jun 2019

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