ArticleScientific reports2020
Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 55 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 regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Local GPCR density tips the balance of μ-opioid receptor trafficking.bioRxiv : the preprint server for biology · 2026Article
- β-Arrestin 1 Differentially Modulates cAMP and ERK Pathways Downstream of the FSH Receptor.Current issues in molecular biology · 2025Article
- Serotonin 5-HTACS chemical neuroscience · 2025Article
- MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor.Nature communications · 2025Article
- Carfentanil stabilizes µ opioid receptor conformations that are ultra-efficient in inhibiting cAMP, resistant to naloxone or nalmefene but sensitive to naltrexone.Archives of toxicology · 2025Article
- Arrestin-independent internalization of the GLP-1 receptor is facilitated by a GRK, clathrin, and caveolae-dependent mechanism.The FEBS journal · 2025Article
- The N-Linked Glycosylation Asn191 and Asn199 Sites Are Controlled Differently Between PKA Signal Transduction and pEKR1/2 Activity in Equine Follicle-Stimulating Hormone Receptor.Current issues in molecular biology · 2025Article
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology.Journal of cell science · 2025Review
- Role of the G protein-coupled receptor kinase 2/3 N terminus in discriminating the endocytic effects of opioid agonist drugs.Molecular pharmacology · 2025Article
- Characterization of Trileucine Motif in the C-Terminus of the Equine Lutropin/Choriogonadotropin Receptor.Current issues in molecular biology · 2024Article
- Key phosphorylation sites for robust β-arrestin2 binding at the MOR revisited.Communications biology · 2024Article
- GRK specificity and Gβγ dependency determines the potential of a GPCR for arrestin-biased agonism.Communications biology · 2024Article
- Stable Production of a Tethered Recombinant Eel Luteinizing Hormone Analog with High Potency in CHO DG44 Cells.Current issues in molecular biology · 2024Article
- GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization.Science signaling · 2024Article
- G Protein-Coupled Receptor Kinase 2 Selectively Enhances β-Arrestin Recruitment to the DBiomolecules · 2023Article
- Atypical Chemokine Receptor 3 "Senses" CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.Molecular pharmacology · 2023Article
- Atypical Chemokine Receptor 3 'Senses' CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Most G protein-coupled receptors (GPCRs) recruit β-arrestins and internalize upon agonist stimulation. For the μ-opioid receptor (μ-OR), this process has been linked to development of opioid tolerance. GPCR kinases (GRKs), particularly GRK2 and GRK3, have been shown to be important for μ-OR recruitment of β-arrestin and internalization. However, the contribution of GRK2 and GRK3 to β-arrestin recruitment and receptor internalization, remain to be determined in their complete absence. Using CRISPR/Cas9-mediated genome editing we established HEK293 cells with knockout of GRK2, GRK3 or both to dissect their individual contributions in β-arrestin2 recruitment and μ-OR internalization upon stimulation with four different agonists. We showed that GRK2/3 removal reduced agonist-induced μ-OR internalization and β-arrestin2 recruitment substantially and we found GRK2 to be more important for these processes than GRK3. Furthermore, we observed a sustained and GRK2/3 independent component of β-arrestin2 recruitment to the plasma membrane upon μ-OR activation. Rescue expression experiments restored GRK2/3 functions. Inhibition of GRK2/3 using the small molecule inhibitor CMPD101 showed a high similarity between the genetic and pharmacological approaches, cross-validating the specificity of both. However, off-target effects were observed at high CMPD101 concentrations. These GRK2/3 KO cell lines should prove useful for a wide range of studies on GPCR function.
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.