ArticleThe EMBO journal2001
Beta-arrestin- and c-Src-dependent degradation of G-protein-coupled receptor kinase 2.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 136 citations in OpenAlex.
- EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2-Mediated µ-Opioid Receptor Internalization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- G-Protein-Coupled Receptor Kinase 2 Limits CCL21-Induced T Cell Migration via Phospholipase Cγ1.Receptors (Basel, Switzerland) · 2025Article
- Mdm2-Mediated Ubiquitination Plays a Pivotal Role in Differentiating the Endocytic Roles of GRK2 and Arrestin3.International journal of molecular sciences · 2025Article
- GRK2-mediated AKT activation controls cell cycle progression and G2 checkpoint in a p53-dependent manner.Cell death discovery · 2024Article
- Astragaloside IV protects brain cells from ischemia-reperfusion injury by inhibiting ryanodine receptor expression and reducing the expression of P-Src and P-GRK2.Scientific reports · 2024Article
- GPCR targeting of E3 ubiquitin ligase MDM2 by inactive β-arrestin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- 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
- Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost.International journal of molecular sciences · 2022Review
- How Arrestins and GRKs Regulate the Function of Long Chain Fatty Acid Receptors.International journal of molecular sciences · 2022Review
- Double life: How GRK2 and β-arrestin signaling participate in diseases.Cellular signalling · 2022Review
- Review
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- Nitric Oxide and S-Nitrosylation in Cardiac Regulation: G Protein-Coupled Receptor Kinase-2 and β-Arrestins as Targets.International journal of molecular sciences · 2021Review
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- Modulation of CXCR4-Mediated Gi1 Activation by EGF Receptor and GRK2.ACS pharmacology & translational science · 2020Article
- β-Arrestin2 is a critical component of the GPCR-eNOS signalosome.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- GRK2-Dependent HuR Phosphorylation Regulates HIF1α Activation under Hypoxia or Adrenergic Stress.Cancers · 2020Article
- Autophagy mediates hepatic GRK2 degradation to facilitate glucagon-induced metabolic adaptation to fasting.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Signal Transduction Profiling of Angiotensin II Type 1 Receptor With Mutations Associated to Atrial Fibrillation in Humans.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G-protein-coupled receptor kinase 2 (GRK2) plays a key role in the regulation of G-protein-coupled receptors (GPCRs). GRK2 expression is altered in several pathological conditions, but the molecular mechanisms that modulate GRK2 cellular levels are largely unknown. We recently have described that GRK2 is degraded rapidly by the proteasome pathway. This process is enhanced by GPCR stimulation and is severely impaired in a GRK2 mutant that lacks kinase activity (GRK2-K220R). In this report, we find that beta-arrestin function and Src-mediated phosphorylation of GRK2 are critically involved in GRK2 proteolysis. Overexpression of beta-arrestin triggers GRK2-K220R degradation based on its ability to recruit c-Src, since this effect is not observed with beta-arrestin mutants that display an impaired c-Src interaction. The presence of an inactive c-Src mutant or of tyrosine kinase inhibitors strongly inhibits co-transfected or endogenous GRK2 turnover, respectively, and a GRK2 mutant with impaired phosphorylation by c-Src shows a markedly retarded degradation. This pathway for the modulation of GRK2 protein stability puts forward a new feedback mechanism for regulating GRK2 levels and GPCR signaling.
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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.