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Nuclear G Protein Signaling

New Tricks for Old Dogs

Campden, Rhiannon BSc; Audet, Nicolas PhD; Hébert, Terence E. PhD

Journal of Cardiovascular Pharmacology: February 2015 - Volume 65 - Issue 2 - p 110–122
doi: 10.1097/FJC.0000000000000198
Invited Review Article

Abstract: According to the standard model of G protein–coupled receptor (GPCR) signaling, GPCRs are localized to the cell membrane where they respond to extracellular signals. Stimulation of GPCRs leads to the activation of heterotrimeric G proteins and their intracellular signaling pathways. However, this model fails to accommodate GPCRs, G proteins, and their downstream effectors that are found on the nuclear membrane or in the nucleus. Evidence from isolated nuclei indicates the presence of GPCRs on the nuclear membrane that can activate similar G protein–dependent signaling pathways in the nucleus as at the cell surface. These pathways also include activation of cyclic adenosine monophosphate, calcium and nitric oxide synthase signaling in cardiomyocytes. In addition, a number of distinct heterotrimeric and monomeric G proteins have been found in the nucleus of various cell types. This review will focus on understanding the function of nuclear G proteins with a focus on cardiac signaling where applicable.

Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada.

Reprints: Terence E. Hébert, PhD, Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1303, Montréal, Québec, Canada H3G 1Y6 (e-mail:

Supported by grants from the Canadian Institutes of Health Research (CIHR; MOP-79354 to T. E. Hébert). N. Audet holds a postdoctoral fellowship from the McGill-CIHR Drug Development Training Program (DDTP). R. Campden holds a graduate studentship from the National Science and Engineering Research Council of Canada (NSERC).

The authors report no conflicts of interest.

R. Campden and N. Audet contributed equally to the study.

Received August 08, 2014

Accepted November 14, 2014

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