ArticleCirculation research2011
p63RhoGEF couples Gα(q/11)-mediated signaling to Ca2+ sensitization of vascular smooth muscle contractility.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
- Research Progress on the ARHGEF Family in Cardiovascular Diseases.Cell biochemistry and function · 2026Review
- A Novel Single-Color FRET Sensor for Rho-Kinase Reveals Calcium-Dependent Activation of RhoA and ROCK.Sensors (Basel, Switzerland) · 2024Article
- Dual thick and thin filament linked regulation of stretch- and L-NAME-induced tone in young and senescent murine basilar artery.Frontiers in physiology · 2023Article
- Epoxyeicosatrienoic Acid and Prostanoid Crosstalk at the Receptor and Intracellular Signaling Levels to Maintain Vascular Tone.International journal of molecular sciences · 2022Article
- Coronary Artery Spasm: Risk Factors, Pathophysiological Mechanisms and Novel Diagnostic Approaches.Reviews in cardiovascular medicine · 2022Review
- Inhibition of Human Prostate and Bladder Smooth Muscle Contraction, Vasoconstriction of Porcine Renal and Coronary Arteries, and Growth-Related Functions of Prostate Stromal Cells by Presumed Small Molecule GαFrontiers in physiology · 2022Article
- Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT.Biomedicines · 2020Review
- Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.PLoS biology · 2020Article
- Article
- Structural design principles that underlie the multi-specific interactions of GαScientific reports · 2019Article
- Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.Pharmacology & therapeutics · 2019Review
- Targeting G protein-coupled receptor signalling by blocking G proteins.Nature reviews. Drug discovery · 2018Review
- Role of age, Rho-kinase 2 expression, and G protein-mediated signaling in the myogenic response in mouse small mesenteric arteries.Physiological reports · 2018Article
- Gαq/p63RhoGEF interaction in RhoA/Rho kinase signaling: investigation in Gitelman's syndrome and implications with hypertension.Journal of endocrinological investigation · 2018Article
- Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis.British journal of pharmacology · 2017Article
- ROK and Arteriolar Myogenic Tone Generation: Molecular Evidence in Health and Disease.Frontiers in pharmacology · 2017Review
- Kinetics of recruitment and allosteric activation of ARHGEF25 isoforms by the heterotrimeric G-protein Gαq.Scientific reports · 2016Article
- GPR78 promotes lung cancer cell migration and metastasis by activation of Gαq-Rho GTPase pathway.BMB reports · 2016Article
- Heme Oxygenases in Cardiovascular Health and Disease.Physiological reviews · 2016Review
- Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease.British journal of pharmacology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleIn normal and diseased vascular smooth muscle (SM), the RhoA pathway, which is activated by multiple agonists through G protein-coupled receptors (GPCRs), plays a central role in regulating basal tone and peripheral resistance. This occurs through inhibition of myosin light chain phosphatase, leading to increased phosphorylation of the myosin regulatory light chain. Although it is thought that specific agonists and GPCRs may couple to distinct RhoA guanine nucleotide exchange factors (GEFs), thus raising the possibility of selective targeting of specific GEFs for therapeutic use, this notion is largely unexplored for SM contraction.
objectiveWe examine whether p63RhoGEF, known to couple specifically to Gα(q/11) in vitro, is functional in blood vessels as a mediator of RhoA activation and if it is selectively activated by Gα(q/11) coupled agonists. METHODS AND
resultsWe find that p63RhoGEF is present across SM tissues and demonstrate that silencing of the endogenous p63RhoGEF in mouse portal vein inhibits contractile force induced by endothelin-1 to a greater extent than the predominantly Gα(12/13)-mediated thromboxane analog U46619. This is because endothelin-1 acts on Gα(q/11) as well as Gα(12/13). Introduction of the exogenous isolated pleckstrin-homology (PH) domain of p63RhoGEF (residues 331-580) into permeabilized rabbit portal vein inhibited Ca2+ sensitized force and activation of RhoA, when phenylephrine was used as an agonist. This reinforces the results based on endothelin-1, because phenylephrine is thought to act exclusively through Gα(q/11).
conclusionWe demonstrate that p63RhoGEF selectively couples Gα(q/11) but not Gα(12/13), to RhoA activation in blood vessels and cultured cells and thus mediates the physiologically important Ca2+ sensitization of force induced with Gα(q/11)-coupled agonists. Our results suggest that signaling through p63RhoGEF provides a novel mechanism for selective regulation of blood pressure.
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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.