ArticlePloS one2013
Nuclear translocation of cardiac G protein-Coupled Receptor kinase 5 downstream of select Gq-activating hypertrophic ligands is a calmodulin-dependent process.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 71 citations in OpenAlex.
- Calmodulin assists during co-translational folding of the KProtein science : a publication of the Protein Society · 2026Article
- High-Throughput Cardiac Hypertrophy Phenotyping Supports Lead Optimization of GRK5 Inhibitors.ACS medicinal chemistry letters · 2026Article
- Dynamic integrin expression, atypical nuclear localization, and spatial distribution during ovarian cancer progression and metastasis.Frontiers in cell and developmental biology · 2026Article
- Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction.International journal of molecular sciences · 2025Article
- Potent, Selective, and Drug-Like G Protein-Coupled Receptor Kinase 5 and 6 Inhibitors: Design, Synthesis, and X-Ray Structural Studies.ChemMedChem · 2025Article
- Design, synthesis, and X-ray structural studies of a series of highly potent, selective, and drug-like G protein-coupled receptor kinase 5 inhibitors.European journal of medicinal chemistry · 2025Article
- Effect of Clinical and Genetic Factors on the Development of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG) in Egyptian Patients Receiving Beta-Blockers.Cardiovascular drugs and therapy · 2024Article
- Development of a new class of potent and highly selective G protein-coupled receptor kinase 5 inhibitors and structural insight from crystal structures of inhibitor complexes.European journal of medicinal chemistry · 2024Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- GRK5-mediated inflammation and fibrosis exert cardioprotective effects during the acute phase of myocardial infarction.FEBS open bio · 2023Article
- G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022Review
- Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.JACC. Basic to translational science · 2022Article
- Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling.EMBO reports · 2021Article
- On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart.Cellular signalling · 2021Review
- A peptide of the N terminus of GRK5 attenuates pressure-overload hypertrophy and heart failure.Science signaling · 2021Article
- G protein-coupled receptor kinase 2 modifies the cellular reaction to cisplatin through interactions with NADPH oxidase 4.Molecular and cellular biochemistry · 2021Article
- Targeting GRK5 for Treating Chronic Degenerative Diseases.International journal of molecular sciences · 2021Review
- GRK5 is a regulator of fibroblast activation and cardiac fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- Structure of a GRK5-Calmodulin Complex Reveals Molecular Mechanism of GRK Activation and Substrate Targeting.Molecular cell · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
G protein-Coupled Receptors (GPCRs) kinases (GRKs) play a crucial role in regulating cardiac hypertrophy. Recent data from our lab has shown that, following ventricular pressure overload, GRK5, a primary cardiac GRK, facilitates maladaptive myocyte growth via novel nuclear localization. In the nucleus, GRK5's newly discovered kinase activity on histone deacetylase 5 induces hypertrophic gene transcription. The mechanisms governing the nuclear targeting of GRK5 are unknown. We report here that GRK5 nuclear accumulation is dependent on Ca(2+)/calmodulin (CaM) binding to a specific site within the amino terminus of GRK5 and this interaction occurs after selective activation of hypertrophic Gq-coupled receptors. Stimulation of myocytes with phenylephrine or angiotensinII causes GRK5 to leave the sarcolemmal membrane and accumulate in the nucleus, while the endothelin-1 does not cause nuclear GRK5 localization. A mutation within the amino-terminus of GRK5 negating CaM binding attenuates GRK5 movement from the sarcolemma to the nucleus and, importantly, overexpression of this mutant does not facilitate cardiac hypertrophy and related gene transcription in vitro and in vivo. Our data reveal that CaM binding to GRK5 is a physiologically relevant event that is absolutely required for nuclear GRK5 localization downstream of hypertrophic stimuli, thus facilitating GRK5-dependent regulation of maladaptive hypertrophy.
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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.