ArticleCirculation. Heart failure2011
Nuclear effects of G-protein receptor kinase 5 on histone deacetylase 5-regulated gene transcription in heart failure.
Article in Circulation. Heart failure, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Comparative Phosphoproteomic Profiling and Network-based Interactome Analysis of GRK5 and GRK6.Cell biochemistry and biophysics · 2026Article
- Chronic β-Blockade and Systemic Homeostasis: Molecular Integration of Cardiorenal and Immune Pathways, a Narrative Review.Biomolecules · 2025Review
- KLF9-GRK5-HDAC6 axis aggravates osteoarthritis pathogenesis by promoting chondrocyte extracellular matrix degradation and apoptosis.Communications biology · 2025Article
- GRK5-mediated inflammation and fibrosis exert cardioprotective effects during the acute phase of myocardial infarction.FEBS open bio · 2023Article
- Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling.EMBO reports · 2021Article
- The genetics of cardiac failure: Role of a G protein-coupled receptor polymorphism in therapeutic response in an Indian population.Journal of clinical and translational research · 2021Article
- A peptide of the N terminus of GRK5 attenuates pressure-overload hypertrophy and heart failure.Science signaling · 2021Article
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure.Biomolecules & therapeutics · 2020Article
- Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal.Oncotarget · 2020Article
- RNAs and Gene Expression Predicting Postoperative Atrial Fibrillation in Cardiac Surgery Patients Undergoing Coronary Artery Bypass Grafting.Journal of clinical medicine · 2020Review
- β-Adrenergic receptor, an essential target in cardiovascular diseases.Heart failure reviews · 2020Review
- Designer Approaches for G Protein-Coupled Receptor Modulation for Cardiovascular Disease.JACC. Basic to translational science · 2018Review
- PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) regulates G-protein-coupled receptor kinase 5 (GRK5)-induced cardiac hypertrophyThe Journal of biological chemistry · 2018Article
- GRK5 - A Functional Bridge Between Cardiovascular and Neurodegenerative Disorders.Frontiers in pharmacology · 2018Review
- The Role of G Protein-coupled Receptor Kinases in Cancer.International journal of biological sciences · 2018Review
- Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling.Journal of cardiovascular pharmacology · 2017Review
- Proinflammatory Cytokines Mediate GPCR Dysfunction.Journal of cardiovascular pharmacology · 2017Review
- The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development.Pharmacological research · 2016Review
- G Protein-Coupled Receptor Kinases: Crucial Regulators of Blood Pressure.Journal of the American Heart Association · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundG-protein receptor kinases (GRKs) modulate cardiac β-adrenergic signaling. GRK5 is upregulated in heart failure, and a gain-of-function polymorphism substituting leucine for wild-type glutamine at amino acid 41 (GRK5-Leu41) is associated with improved outcomes in heart failure and hypertension. GRK5 is distinguished by partial nuclear localization and class II histone deacetylases (HDAC) kinase activity that is postulated to regulate Gαq-stimulated cardiac gene expression. METHODS AND
resultsWe used in vitro tissue culture and in vivo mouse compound genetic models to examine the effects of GRK5 on HDAC phosphorylation, nucleo-cytoplasmic HDAC transport, and Gαq-dependent transcriptional regulation. In vitro, GRK5 stimulated HDAC5 nuclear export only in the context of Gαq signaling stimulated by angiotensin II. GRK5-Gln41 and Leu41 were similar inducers of HDAC5 nucleo-cytoplasmic shuttling. In vivo, GRK5-Gln41 and-Leu41 partitioned equally to nuclear and nonnuclear myocardial fractions. GRK5 increased cardiac HDAC5 phosphorylation and reversed the increase in nuclear HDAC5 content seen with cardiomyocyte-autonomous Gαq overexpression. Deep RNA sequencing showed few changes in gene expression induced by GRK5 overexpression or ablation alone, but GRK5 overexpression normalized steady-state expression levels of 48% (96 of 200) of all Gαq down-regulated mRNAs.
conclusionsGRK5 is a transcriptional modifier of a subset of Gαq-downregulated genes, acting in opposition to the pathological effects of Gαq and normalizing levels of these transcripts. This transcriptional coregulator effect may act in concert with β-adrenergic receptor desensitization to protect against heart failure decompensation.
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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.