ArticleMolecular cell2015
A Non-Canonical Function of Gβ as a Subunit of E3 Ligase in Targeting GRK2 Ubiquitylation.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- The GRK2/AP-1 Signaling Axis Mediates Vascular Endothelial Dysfunction and Atherosclerosis Induced by Oscillatory Low Shear Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- 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
- Cohesin: an emerging master regulator at the heart of cardiac development.Molecular biology of the cell · 2023Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Lactate increases tumor malignancy by promoting tumor small extracellular vesicles productionFrontiers in oncology · 2022Article
- Extracellular calcium alters calcium-sensing receptor network integrating intracellular calcium-signaling and related key pathway.Scientific reports · 2021Article
- Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.PLoS genetics · 2021Article
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
- Inhibition of CLU4A exhibits a cardioprotective role in hypoxia/reoxygenation-induced injury by an ERK-dependent pathway.International journal of clinical and experimental pathology · 2019Article
- Single Nucleotide Polymorphisms in Chemosensory Pathway Genes GNB3, TAS2R19, and TAS2R38 Are Associated with Chronic Rhinosinusitis.International archives of allergy and immunology · 2019Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Regulation of Smoothened ubiquitylation and cell surface expression through a Cul4-DDB1-Gβ E3 ubiquitin ligase complex.Journal of cell science · 2018Article
- Functional analysis of Cullin 3 E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- A cullin 4B-RING E3 ligase complex fine-tunes pancreatic δ cell paracrine interactions.The Journal of clinical investigation · 2017Article
- Saxagliptin Attenuates Albuminuria by Inhibiting Podocyte Epithelial- to-Mesenchymal Transition via SDF-1α in Diabetic Nephropathy.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) comprise the largest family of cell surface receptors, regulate a wide range of physiological processes, and are the major targets of pharmaceutical drugs. Canonical signaling from GPCRs is relayed to intracellular effector proteins by trimeric G proteins, composed of α, β, and γ subunits (Gαβγ). Here, we report that G protein β subunits (Gβ) bind to DDB1 and that Gβ2 targets GRK2 for ubiquitylation by the DDB1-CUL4A-ROC1 ubiquitin ligase. Activation of GPCR results in PKA-mediated phosphorylation of DDB1 at Ser645 and its dissociation from Gβ2, leading to increase of GRK2 protein. Deletion of Cul4a results in cardiac hypertrophy in male mice that can be partially rescued by the deletion of one Grk2 allele. These results reveal a non-canonical function of the Gβ protein as a ubiquitin ligase component and a mechanism of feedback regulation of GPCR signaling.
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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.