ArticlePloS one2013
Distinct structural features of G protein-coupled receptor kinase 5 (GRK5) regulate its nuclear localization and DNA-binding ability.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- G protein‑coupled receptor kinase 4 governs early kidney development via STAT3 and Nhe3a.International journal of molecular medicine · 2026Article
- Comparative Phosphoproteomic Profiling and Network-based Interactome Analysis of GRK5 and GRK6.Cell biochemistry and biophysics · 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
- Ubiquitination of GRK2 Is Required for the β-Arrestin-Biased Signaling Pathway of Dopamine D2 Receptors to Activate ERK Kinases.International journal of molecular sciences · 2023Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.International journal of molecular sciences · 2022Review
- Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.JACC. Basic to translational science · 2022Article
- A peptide of the N terminus of GRK5 attenuates pressure-overload hypertrophy and heart failure.Science signaling · 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
- Review
- Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal.Oncotarget · 2020Article
- 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
- G protein-coupled receptor kinase 4-induced cellular senescence and its senescence-associated gene expression profiling.Experimental cell research · 2017Article
- Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling.Journal of cardiovascular pharmacology · 2017Review
- G Protein-Coupled Receptor Kinases: Crucial Regulators of Blood Pressure.Journal of the American Heart Association · 2016Review
- Ras-activated RSK1 phosphorylates EBP50 to regulate its nuclear localization and promote cell proliferation.Oncotarget · 2016Article
- "Canonical and non-canonical actions of GRK5 in the heart".Journal of molecular and cellular cardiology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor kinases (GRKs) act to desensitize G protein-coupled receptors (GPCRs). In addition to this role at the plasma membrane, a nuclear function for GRK5, a member of the GRK4 subfamily of GRKs, has been reported. GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5. Here we demonstrate that the possession of a nuclear localization sequence (NLS) is a common feature of GRK4 subfamily members (GRKs 4, 5 and 6). However, the location of the NLS and the ability of these GRKs to bind DNA in vitro are different. The NLSs of GRK5 and 6 bind DNA in vitro, whilst the NLS of GRK4 does not. Using mutants of GRK5 we identify the regions of GRK5 required for DNA-binding in vitro and nuclear localization in cells. The DNA-binding ability of GRK5 requires both the NLS and an N-terminal calmodulin (CaM)-binding site. A functional nuclear export sequence (NES), required for CaM-dependent nuclear export of the kinase, is also identified. Based on our observations we propose a model to explain how nuclear localization of GRK5 may be regulated. Notably, the nuclear localization of GRK5 and 6 is differentially regulated. These results suggest subfamily specific nuclear functions for the GRK4 subfamily members. Identification of GRK specific small molecule inhibitors of nuclear localization and/or function for the GRK4 subfamily may thus be an achievable goal.
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