Complex Formation between VEGFR2 and the β-Adrenoceptor.

Authors:
Laura E Kilpatrick
Laura E Kilpatrick
School of Biomedical Sciences
Diana C Alcobia
Diana C Alcobia
School of Life Sciences
Tempe | United States
Carl W White
Carl W White
University of Colorado Denver
United States
Chloe J Peach
Chloe J Peach
School of Life Sciences
Tempe | United States
Jackie R Glenn
Jackie R Glenn
University of Nottingham
United Kingdom
Kris Zimmerman
Kris Zimmerman
Promega Corporation
Alexander Kondrashov
Alexander Kondrashov
School of Pharmacy
United Kingdom

Cell Chem Biol 2019 Mar 14. Epub 2019 Mar 14.

Division 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. Electronic address:

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 β-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 β-adrenoceptor to β-arrestin2 is prolonged by VEGFR2 activation. These data suggest that protein-protein interactions between VEGFR2, the β-adrenoceptor, and β-arrestin2 may provide insight into their roles in health and disease.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chembiol.2019.02.014DOI Listing
March 2019
1 Read

Publication Analysis

Top Keywords

vegfr2 β-adrenoceptor
12
vascular endothelial
8
β-adrenoceptor β-arrestin2
8
vegfr2
7
β-adrenoceptor
5
luciferase demonstrate
4
nanoluc luciferase
4
demonstrate oligomeric
4
genetically tagged
4
vegfr2 genetically
4
tagged nanoluc
4
complexes involving
4
cell membranes
4
generated cell
4
β-adrenoceptor generated
4
involving vegfr2
4
oligomeric complexes
4
resonance energy
4
β-adrenoceptor antagonist
4
antagonist propranolol
4

Similar Publications