ArticleScience signaling2011
Quantitative encoding of the effect of a partial agonist on individual opioid receptors by multisite phosphorylation and threshold detection.
Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 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
75 citing papers in PubMed, 108 citations in OpenAlex.
- Lysosomal down-regulation of the mu opioid receptor is opposed by the Retromer complex.Science advances · 2026Article
- Role of the G protein-coupled receptor kinase 2/3 N terminus in discriminating the endocytic effects of opioid agonist drugs.Molecular pharmacology · 2025Article
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Profiling the proximal proteome of the activated μ-opioid receptor.Nature chemical biology · 2024Article
- Key phosphorylation sites for robust β-arrestin2 binding at the MOR revisited.Communications biology · 2024Article
- Arrestins: A Small Family of Multi-Functional Proteins.International journal of molecular sciences · 2024Review
- Cannabinoid 1 (CBBritish journal of pharmacology · 2023Article
- Article
- An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation.Journal of visualized experiments : JoVE · 2022Article
- Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward.Frontiers in systems neuroscience · 2022Review
- Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene,Biomolecules · 2021Review
- Molecular mechanisms of opioid tolerance: From opioid receptors to inflammatory mediators (Review).Experimental and therapeutic medicine · 2021Review
- Mechanisms of selective G protein-coupled receptor localization and trafficking.Current opinion in cell biology · 2021Review
- Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis.Annual review of biochemistry · 2021Review
- Proteomic Approaches to Investigate Regulated Trafficking and Signaling of G Protein-Coupled Receptors.Molecular pharmacology · 2021Review
- The Pharmacology of Buprenorphine Microinduction for Opioid Use Disorder.Clinical drug investigation · 2021Review
- Review
- Review
- Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells.Scientific reports · 2020Article
- Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.Molecular pharmacology · 2020Article
15 more citing papers are in PubMed but not listed here.
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 1 institution in 1 country.
Funding
Abstract
In comparison to endogenous ligands of seven-transmembrane receptors, which typically act as full agonists, many drugs act as partial agonists. Partial agonism is best described as a "macroscopic" property that is manifest at the level of physiological systems or cell populations; however, whether partial agonists also encode discrete regulatory information at the "microscopic" level of individual receptors is not known. Here, we addressed this question by focusing on morphine, a partial agonist drug for μ-type opioid peptide receptors (MORs), and by combining quantitative mass spectrometry with cell biological analysis to investigate the reduced efficacy of morphine, compared to that of a peptide full agonist, in promoting receptor endocytosis. We showed that these chemically distinct ligands produced a complex and qualitatively similar mixture of phosphorylated opioid receptor forms in intact cells. Quantitatively, however, the different agonists promoted disproportionate multisite phosphorylation of a specific serine and threonine motif, and we found that modification at more than one residue was essential for the efficient recruitment of the adaptor protein β-arrestin that mediated subsequent endocytosis of MORs. Thus, quantitative encoding of agonist-selective endocytosis at the level of individual opioid receptors was based on the conserved biochemical principles of multisite phosphorylation and threshold detection.
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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.