ArticleThe Journal of biological chemistry2011
Protein kinase Czeta mediates micro-opioid receptor-induced cross-desensitization of chemokine receptor CCR5.
Article in The Journal of biological chemistry, 2011. 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, 32 citations in OpenAlex.
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- Recent Synthesis, Characterization, and Pharmacological Evaluation of Multifunctional Hemorphins Containing Non-Natural Amino Acids with Potential Biological Importance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Kappa Opioid Receptor Expression and Function in Cells of the Immune System.Handbook of experimental pharmacology · 2022Article
- The μ-opioid receptor induces miR-21 expression and is ERK/PKCμ-dependent.Journal of neuroimmunology · 2021Article
- Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity.Journal of medicinal chemistry · 2021Article
- Review
- Chemokines, cytokines and substance use disorders.Drug and alcohol dependence · 2021Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Conditional expression of HIV-1 tat in the mouse alters the onset and progression of tonic, inflammatory and neuropathic hypersensitivity in a sex-dependent manner.European journal of pain (London, England) · 2020Article
- Bidirectional Regulation of Opioid and Chemokine Function.Frontiers in immunology · 2020Review
- The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward.Neuropharmacology · 2019Article
- The Role of Opioid Receptors in Immune System Function.Frontiers in immunology · 2019Review
- Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease.Pain · 2018Article
- CCR5 mediates HIV-1 Tat-induced neuroinflammation and influences morphine tolerance, dependence, and reward.Brain, behavior, and immunity · 2018Article
- Central HIV-1 Tat exposure elevates anxiety and fear conditioned responses of male mice concurrent with altered mu-opioid receptor-mediated G-protein activation and β-arrestin 2 activity in the forebrain.Neurobiology of disease · 2016Article
- Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10.British journal of pharmacology · 2014Review
- Cross-desensitization of CCR1, but not CCR2, following activation of the formyl peptide receptor FPR1.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.International review of neurobiology · 2014Review
- A novel bivalent HIV-1 entry inhibitor reveals fundamental differences in CCR5-μ-opioid receptor interactions between human astroglia and microglia.AIDS (London, England) · 2013Article
- Polymorphisms of the kappa opioid receptor and prodynorphin genes: HIV risk and HIV natural history.Journal of acquired immune deficiency syndromes (1999) · 2013Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
We have previously shown that the μ-opioid receptor (MOR) is capable of mediating cross-desensitization of several chemokine receptors including CCR5, but the biochemical mechanism of this process has not been fully elucidated. We have carried out a series of functional and biochemical studies and found that the mechanism of MOR-induced cross-desensitization of CCR5 involves the activation of PKCζ. Inhibition of PKCζ by its pseudosubstrate inhibitor, or its siRNA, or dominant negative mutants suppresses the cross-desensitization of CCR5. Our results further indicate that the activation of PKCζ is mediated through a pathway involving phosphoinositol-dependent kinase-1 (PDK1). In addition, activation of MOR elevates the phosphorylation level and kinase activity of PKCζ. The phosphorylation of PKCζ can be suppressed by a dominant negative mutant of PDK1. We observed that following MOR activation, the interaction between PKCζ and PDK1 is immediately increased based on the analysis of fluorescent resonance energy transfer in cells with the expression of PKCζ-YFP and PDK1-CFP. In addition, cells expressing PKCζ kinase motif mutants (Lys-281, Thr-410, Thr-560) fail to exhibit full MOR-induced desensitization of CCR5 activity. Taken together, we propose that upon DAMGO treatment, MOR activates PKCζ through a PDK1-dependent signaling pathway to induce CCR5 phosphorylation and desensitization. Because CCR5 is a highly proinflammatory receptor, and a critical coreceptor for HIV-1, these results may provide a novel approach for the development of specific therapeutic agents to treat patients with certain inflammatory diseases or AIDS.
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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 Socratic graph.