ArticleBritish journal of pharmacology2014
Heterologous regulation of agonist-independent μ-opioid receptor phosphorylation by protein kinase C.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Key phosphorylation sites for robust β-arrestin2 binding at the MOR revisited.Communications biology · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- Microglial inflammation modulates opioid analgesic tolerance.Journal of neuroscience research · 2023Review
- In situ visualization of opioid and cannabinoid drug effects using phosphosite-specific GPCR antibodies.Communications biology · 2023Article
- A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening.Communications biology · 2022Article
- Delineating the interactions between the cannabinoid CBBritish journal of pharmacology · 2022Article
- High-throughput screening and validation of antibodies against synaptic proteins to explore opioid signaling dynamics.Communications biology · 2021Article
- Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.Nature communications · 2021Article
- Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.Molecular pharmacology · 2020Article
- A cellular perspective of bias at G protein-coupled receptors.Protein science : a publication of the Protein Society · 2020Review
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- Agonist-induced phosphorylation bar code and differential post-activation signaling of the delta opioid receptor revealed by phosphosite-specific antibodies.Scientific reports · 2020Article
- Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection.International journal of molecular sciences · 2019Review
- Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists.Science signaling · 2019Article
- Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects.Nature communications · 2019Article
- Activation of the G Protein-Coupled Estrogen Receptor Elicits Store Calcium Release and Phosphorylation of the Mu-Opioid Receptors in the Human Neuroblastoma SH-SY5Y Cells.Frontiers in neuroscience · 2019Article
- Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia.British journal of pharmacology · 2018Article
- Article
- Agonist-Dependent and -Independent κ Opioid Receptor Phosphorylation: Distinct Phosphorylation Patterns and Different Cellular Outcomes.Molecular pharmacology · 2017Article
- Conventional protein kinase C in the brain: 40 years later.Neuronal signaling · 2017Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHomologous agonist-induced phosphorylation of the μ-opioid receptor (MOR) is initiated at the carboxyl-terminal S375, followed by phosphorylation of T370, T376 and T379. In HEK293 cells, this sequential and hierarchical multi-site phosphorylation is specifically mediated by G-protein coupled receptor kinases 2 and 3. In the present study, we provide evidence for a selective and dose-dependent phosphorylation of T370 after activation of PKC by phorbol esters. EXPERIMENTAL APPROACH: We used a combination of phospho site-specific antibodies, kinase inhibitors and siRNA knockdown screening to identify kinases that mediate agonist-independent phosphorylation of the MOR in HEK293 cells. In addition, we show with phospho site-specific antibodies were also used to study constitutive phosphorylation at S363 of MORs in mouse brain in vivo. KEY
resultsActivation of PKC by phorbol esters or heterologous activation of substance P receptors co-expressed with MORs in the same cell induced a selective and dose-dependent phosphorylation of T370 that specifically requires the PKCα isoform. Inhibition of PKC activity did not compromise homologous agonist-driven T370 phosphorylation. In addition, S363 was constitutively phosphorylated in both HEK293 cells and mouse brain in vivo. Constitutive S363 phosphorylation required ongoing PKC activity. When basal PKC activity was decreased, S363 was also a substrate for homologous agonist-stimulated phosphorylation. CONCLUSIONS AND IMPLICATIONS: Our results have disclosed novel mechanisms of heterologous regulation of MOR phosphorylation by PKC. These findings represent a useful starting point for definitive experiments elucidating the exact contribution of PKC-driven MOR phosphorylation to diminished MOR responsiveness in morphine tolerance and pathological pain.
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