ArticleThe Journal of biological chemistry2008
Assembly of high order G alpha q-effector complexes with RGS proteins.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- A Rasa3-Gαi signaling axis orchestrates B lymphocyte trafficking into and through lymphoid organs.Cell reports · 2026Article
- Control of GαScience advances · 2022Article
- GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12.Blood advances · 2022Article
- Regulator of G protein signaling 2 inhibits GαThe Journal of biological chemistry · 2022Article
- Gαq/p63RhoGEF interaction in RhoA/Rho kinase signaling: investigation in Gitelman's syndrome and implications with hypertension.Journal of endocrinological investigation · 2018Article
- The Role of G-proteins and G-protein Regulating Proteins in Depressive Disorders.Frontiers in pharmacology · 2018Review
- Protein Kinase C ζ Interacts with a Novel Binding Region of Gαq to Act as a Functional Effector.The Journal of biological chemistry · 2016Article
- Structure of the Regulator of G Protein Signaling 8 (RGS8)-Gαq Complex: MOLECULAR BASIS FOR Gα SELECTIVITY.The Journal of biological chemistry · 2016Article
- Is the model of signal amplification by GPCRs/GEFs activating multiple GTPases relevant to a broad spectrum of heterotrimeric and RAS superfamily GTPases?Cellular logistics · 2014Article
- The role of HTS in drug discovery at the University of Michigan.Combinatorial chemistry & high throughput screening · 2014Review
- Strike a pose: Gαq complexes at the membrane.Trends in pharmacological sciences · 2014Review
- Modification and functional inhibition of regulator of G-protein signaling 4 (RGS4) by 4-hydroxy-2-nonenal.Chemical research in toxicology · 2013Article
- Structural and functional analysis of the regulator of G protein signaling 2-gαq complex.Structure (London, England : 1993) · 2013Article
- Full-length Gα(q)-phospholipase C-β3 structure reveals interfaces of the C-terminal coiled-coil domain.Nature structural & molecular biology · 2013Article
- A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation.PloS one · 2013Article
- Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility.ACS chemical biology · 2012Article
- p63RhoGEF: a new switch for G(q)-mediated activation of smooth muscle.Trends in cardiovascular medicine · 2012Review
- Mechanism of activation and inactivation of Gq/phospholipase C-β signaling nodes.Chemical reviews · 2011Article
- ET-1 induced Elevation of intracellular calcium in clonal neuronal and embryonic kidney cells involves endogenous endothelin-A receptors linked to phospholipase C through Gα(q/11).Pharmacological research · 2011Article
- An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation.Nature structural & molecular biology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Transmembrane signaling through G alpha(q)-coupled receptors is linked to physiological processes such as cardiovascular development and smooth muscle function. Recent crystallographic studies have shown how G alpha(q) interacts with two activation-dependent targets, p63RhoGEF and G protein-coupled receptor kinase 2 (GRK2). These proteins bind to the effector-binding site of G alpha(q) in a manner that does not appear to physically overlap with the site on G alpha(q) bound by regulator of G-protein signaling (RGS) proteins, which function as GTPase-activating proteins (GAPs). Herein we confirm the formation of RGS-G alpha(q)-GRK2/p63RhoGEF ternary complexes using flow cytometry protein interaction and GAP assays. RGS2 and, to a lesser extent, RGS4 are negative allosteric modulators of Galpha(q) 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 G alpha(q) 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.