ArticleThe Journal of biological chemistry2010
G alpha(q)-mediated activation of GRK2 by mechanical stretch in cardiac myocytes: the role of protein kinase C.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- Cardioprotective Strategies After Ischemia-Reperfusion Injury.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis.European heart journal · 2023Article
- The Role of β-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor.Frontiers in endocrinology · 2019Review
- Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction.JACC. Basic to translational science · 2017Article
- Sub-cellular localization specific SUMOylation in the heart.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Protein kinase C mechanisms that contribute to cardiac remodelling.Clinical science (London, England : 1979) · 2016Review
- Electrical and mechanical stimulation of cardiac cells and tissue constructs.Advanced drug delivery reviews · 2016Review
- An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs.Cellular and molecular life sciences : CMLS · 2015Review
- The evolving impact of g protein-coupled receptor kinases in cardiac health and disease.Physiological reviews · 2015Review
- β-adrenergic receptor-mediated cardiac contractility is inhibited via vasopressin type 1A-receptor-dependent signaling.Circulation · 2014Article
- GRK2 in the heart: a GPCR kinase and beyond.Antioxidants & redox signaling · 2014Review
- Mild hypoxia-induced cardiomyocyte hypertrophy via up-regulation of HIF-1α-mediated TRPC signalling.Journal of cellular and molecular medicine · 2012Article
- Article
- Cardiac actions of protein kinase C isoforms.Physiology (Bethesda, Md.) · 2012Review
- Reverse remodeling in heart failure--mechanisms and therapeutic opportunities.Nature reviews. Cardiology · 2011Review
- Protein kinase Cα as a heart failure therapeutic target.Journal of molecular and cellular cardiology · 2011Review
- G protein coupled receptor kinases as therapeutic targets in cardiovascular disease.Circulation research · 2011Review
- G protein-coupled receptor kinases in normal and failing myocardium.Frontiers in bioscience (Landmark edition) · 2011Review
- Computational models reduce complexity and accelerate insight into cardiac signaling networks.Circulation research · 2011Review
Corrections and comments
- Retraction · 2016-07-01Falsification/Fabrication of Data · Investigation by Company/Institution · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Ricky Malhotra has NIH finding of misconduct
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- Retracted
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor kinase-2 (GRK2) is a critical regulator of beta-adrenergic receptor (beta-AR) signaling and cardiac function. We studied the effects of mechanical stretch, a potent stimulus for cardiac myocyte hypertrophy, on GRK2 activity and beta-AR signaling. To eliminate neurohormonal influences, neonatal rat ventricular myocytes were subjected to cyclical equi-biaxial stretch. A hypertrophic response was confirmed by "fetal" gene up-regulation. GRK2 activity in cardiac myocytes was increased 4.2-fold at 48 h of stretch versus unstretched controls. Adenylyl cyclase activity was blunted in sarcolemmal membranes after stretch, demonstrating beta-AR desensitization. The hypertrophic response to mechanical stretch is mediated primarily through the G alpha(q)-coupled angiotensin II AT(1) receptor leading to activation of protein kinase C (PKC). PKC is known to phosphorylate GRK2 at the N-terminal serine 29 residue, leading to kinase activation. Overexpression of a mini-gene that inhibits receptor-G alpha(q) coupling blunted stretch-induced hypertrophy and GRK2 activation. Short hairpin RNA-mediated knockdown of PKC alpha also significantly attenuated stretch-induced GRK2 activation. Overexpression of a GRK2 mutant (S29A) in cardiac myocytes inhibited phosphorylation of GRK2 by PKC, abolished stretch-induced GRK2 activation, and restored adenylyl cyclase activity. Cardiac-specific activation of PKC alpha in transgenic mice led to impaired beta-agonist-stimulated ventricular function, blunted cyclase activity, and increased GRK2 phosphorylation and activity. Phosphorylation of GRK2 by PKC appears to be the primary mechanism of increased GRK2 activity and impaired beta-AR signaling after mechanical stretch. Cross-talk between hypertrophic signaling at the level of PKC and beta-AR signaling regulated by GRK2 may be an important mechanism in the transition from compensatory ventricular hypertrophy to heart failure.
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Identifiers
What Socratic holds
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 Socratic graph.