ArticleThe Journal of biological chemistry2015
G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Revealing GRK5 Activation Features by Interpretable Machine Learning and Molecular Dynamics Simulation.International journal of molecular sciences · 2026Article
- A heteromeric TRP channel that functions as a WNT-activated G protein-coupled receptor.Nature communications · 2026Article
- A cross-tissue transcriptome-wide association study reveals GRK4 as a novel susceptibility gene for COPD.Scientific reports · 2024Article
- Further investigations on the influence of protein phosphatases on the signaling of muscarinic receptors in the atria of mouse hearts.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.Cell reports. Medicine · 2024Article
- G Protein-Coupled Receptor Kinase 2 Selectively Enhances β-Arrestin Recruitment to the DBiomolecules · 2023Article
- Profiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform.Nature communications · 2023Article
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
- GPCR kinase knockout cells reveal the impact of individual GRKs on arrestin binding and GPCR regulation.Nature communications · 2022Article
- Determining the Effects of Differential Expression of GRKs and β-arrestins on CLR-RAMP Agonist Bias.Frontiers in physiology · 2022Article
- Agonist dependency of the second phase access of β-arrestin 2 to the heteromeric µ-V1b receptor.Scientific reports · 2021Article
- The Open Question of How GPCRs Interact with GPCR Kinases (GRKs).Biomolecules · 2021Article
- Receptor-Arrestin Interactions: The GPCR Perspective.Biomolecules · 2021Review
- Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site.PloS one · 2021Article
- Review
- Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides.International journal of molecular sciences · 2020Article
- Dopamine D2 autoreceptor interactome: Targeting the receptor complex as a strategy for treatment of substance use disorder.Pharmacology & therapeutics · 2020Review
- Spatial regulation of GPR64/ADGRG2 signaling by β-arrestins and GPCR kinases.Annals of the New York Academy of Sciences · 2019Article
- Structural Insights into CB1 Receptor Biased Signaling.International journal of molecular sciences · 2019Review
- The structural basis of the arrestin binding to GPCRs.Molecular and cellular endocrinology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous desensitization of GPCRs. It is widely assumed that most GRKs selectively phosphorylate only active GPCRs. Here, we show that although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of several GPCRs, including β2-adrenergic and M2 muscarinic receptors, which are commonly used as representative models for GPCRs. Agonist-independent GPCR phosphorylation cannot be explained by constitutive activity of the receptor or membrane association of the GRK, suggesting that it is an inherent ability of GRK5/6. Importantly, phosphorylation of the inactive β2-adrenergic receptor enhanced its interactions with arrestins. Arrestin-3 was able to discriminate between phosphorylation of the same receptor by GRK2 and GRK5, demonstrating preference for the latter. Arrestin recruitment to inactive phosphorylated GPCRs suggests that not only agonist activation but also the complement of GRKs in the cell regulate formation of the arrestin-receptor complex and thereby G protein-independent signaling.
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What OpenQuestion 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 OpenQuestion graph.