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Assembly of High Order Gαq-Effector Complexes with RGS Proteins
Journal article   Open access   Peer reviewed

Assembly of High Order Gαq-Effector Complexes with RGS Proteins

Aruna Shankaranarayanan, David M Thal, Valerie M Tesmer, David L Roman, Richard R Neubig, Tohru Kozasa and John J.G Tesmer
The Journal of biological chemistry, Vol.283(50), pp.34923-34934
12/12/2008
DOI: 10.1074/jbc.M805860200
PMCID: PMC2596395
PMID: 18936096
url
https://doi.org/10.1074/jbc.M805860200View
Published (Version of record) Open Access

Abstract

Transmembrane signaling through Gαq-coupled receptors is linked to physiological processes such as cardiovascular development and smooth muscle function. Recent crystallographic studies have shown how Gαq interacts with two activation-dependent targets, p63RhoGEF and G protein-coupled receptor kinase 2 (GRK2). These proteins bind to the effector-binding site of Gαq in a manner that does not appear to physically overlap with the site on Gαq bound by regulator of G-protein signaling (RGS) proteins, which function as GTPase-activating proteins (GAPs). Herein we confirm the formation of RGS-Gαq-GRK2/p63RhoGEF ternary complexes using flow cytometry protein interaction and GAP assays. RGS2 and, to a lesser extent, RGS4 are negative allosteric modulators of Gαq binding to either p63RhoGEF or GRK2. Conversely, GRK2 enhances the GAP activity of RGS4 but has little effect on that of RGS2. Similar but smaller magnitude responses are induced by p63RhoGEF. The fact that GRK2 and p63RhoGEF respond similarly to these RGS proteins supports the hypothesis that GRK2 is a bona fide Gαq effector. The results also suggest that signal transduction pathways initiated by GRK2, such as the phosphorylation of G protein-coupled receptors, and by p63RhoGEF, such as the activation of gene transcription, can be regulated by RGS proteins via both allosteric and GAP mechanisms.

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