ArticleThe Journal of biological chemistry2014
Mapping the putative G protein-coupled receptor (GPCR) docking site on GPCR kinase 2: insights from intact cell phosphorylation and recruitment assays.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 36 citations in OpenAlex.
- Multiple intramolecular triggers converge to preferential G protein coupling in the CBNature communications · 2025Article
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- Article
- Article
- BRET-based effector membrane translocation assay monitors GPCR-promoted and endocytosis-mediated GProceedings of the National Academy of Sciences of the United States of America · 2021Article
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- The Open Question of How GPCRs Interact with GPCR Kinases (GRKs).Biomolecules · 2021Article
- Modulation of CXCR4-Mediated Gi1 Activation by EGF Receptor and GRK2.ACS pharmacology & translational science · 2020Article
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
- Identification of Heteroreceptors Complexes and Signal Transduction Events Using Bioluminescence Resonance Energy Transfer (BRET).Bio-protocol · 2019Article
- G Protein-Coupled Receptor Kinase 2 (GRK2) as a Potential Therapeutic Target in Cardiovascular and Metabolic Diseases.Frontiers in pharmacology · 2019Review
- Engineering allosteric regulation in protein kinases.Science signaling · 2018Article
- The dopamine D2 receptor can directly recruit and activate GRK2 without G protein activation.The Journal of biological chemistry · 2018Article
- G protein-coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog.Science signaling · 2018Article
- The Role of G Protein-coupled Receptor Kinases in Cancer.International journal of biological sciences · 2018Review
- G protein-coupled receptor kinases: Past, present and future.Cellular signalling · 2018Article
- Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma.BMC cancer · 2017Article
- Molecular assembly of rhodopsin with G protein-coupled receptor kinases.Cell research · 2017Article
- G protein-coupled receptor kinases as regulators of dopamine receptor functions.Pharmacological research · 2016Review
- Effect of Lipid Composition on the Membrane Orientation of the G Protein-Coupled Receptor Kinase 2-Gβ1γ2 Complex.Biochemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied receptors initiating the processes of desensitization and β-arrestin-dependent signaling. Interaction of GRKs with activated receptors serves to stimulate their kinase activity. The extreme N-terminal helix (αN), the kinase small lobe, and the active site tether (AST) of the AGC kinase domain have previously been implicated in mediating the allosteric activation. Expanded mutagenesis of the αN and AST allowed us to further assess the role of these two regions in kinase activation and receptor phosphorylation in vitro and in intact cells. We also developed a bioluminescence resonance energy transfer-based assay to monitor the recruitment of GRK2 to activated α(2A)-adrenergic receptors (α(2A)ARs) in living cells. The bioluminescence resonance energy transfer signal exhibited a biphasic response to norepinephrine concentration, suggesting that GRK2 is recruited to Gβγ and α(2A)AR with EC50 values of 15 nM and 8 μM, respectively. We show that mutations in αN (L4A, V7E, L8E, V11A, S12A, Y13A, and M17A) and AST (G475I, V477D, and I485A) regions impair or potentiate receptor phosphorylation and/or recruitment. We suggest that a surface of GRK2, including Leu(4), Val(7), Leu(8), Val(11), and Ser(12), directly interacts with receptors, whereas residues such as Asp(10), Tyr(13), Ala(16), Met(17), Gly(475), Val(477), and Ile(485) are more important for kinase domain closure and activation. Taken together with data on GRK1 and GRK6, our data suggest that all three GRK subfamilies make conserved interactions with G protein-coupled receptors, but there may be unique interactions that influence selectivity.
Indexed as
Identifiers
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.