ArticleNature communications2017
Peroxiredoxin 6 mediates Gαi protein-coupled receptor inactivation by cJun kinase.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Anesthesia unconsciousness recruits dynamic parabrachial activity within a distributed brain-wide ensemble.bioRxiv : the preprint server for biology · 2026Article
- Monitoring in real time and far-red imaging of HNature chemical biology · 2026Article
- G Protein Inactivation as a Mechanism for Addiction Treatment.Biological psychiatry · 2026Article
- Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes.Antioxidants (Basel, Switzerland) · 2025Review
- Molecular mechanisms of inverse agonism via κ-opioid receptor-G protein complexes.Nature chemical biology · 2025Article
- Peroxiredoxin 6 in Stress Orchestration and Disease Interplay.Antioxidants (Basel, Switzerland) · 2025Review
- Kinase-catalyzed biotinylation for discovery and validation of substrates to multispecificity kinases NME1 and NME2.The Journal of biological chemistry · 2024Article
- Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism.Addiction neuroscience · 2024Article
- Ultra-fast genetically encoded sensor for precise real-time monitoring of physiological and pathophysiological peroxide dynamics.Research square · 2024Article
- Structure-guided engineering of a fast genetically encoded sensor for real-time HbioRxiv : the preprint server for biology · 2024Article
- Review
- Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023Review
- The dynorphin/kappa opioid receptor mediates adverse immunological and behavioral outcomes induced by repetitive blast trauma.Journal of neuroinflammation · 2022Article
- 14-3-3γ mediates the long-term inhibition of peripheral kappa opioid receptor antinociceptive signaling by norbinaltorphimine.Neuropharmacology · 2022Article
- Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells.Molecules (Basel, Switzerland) · 2022Article
- Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders.Handbook of experimental pharmacology · 2022Article
- PRDX6: A protein bridging S-palmitoylation and diabetic neuropathy.Frontiers in endocrinology · 2022Article
- KOR Control over Addiction Processing: An Exploration of the Mesolimbic Dopamine Pathway.Handbook of experimental pharmacology · 2022Article
- Release of endogenous dynorphin opioids in the prefrontal cortex disrupts cognition.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- The Roles of Peroxiredoxin 6 in Brain Diseases.Molecular neurobiology · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Inactivation of opioid receptors limits the therapeutic efficacy of morphine-like analgesics and mediates the long duration of kappa opioid antidepressants by an uncharacterized, arrestin-independent mechanism. Here we use an iterative, discovery-based proteomic approach to show that following opioid administration, peroxiredoxin 6 (PRDX6) is recruited to the opioid receptor complex by c-Jun N-terminal kinase (JNK) phosphorylation. PRDX6 activation generates reactive oxygen species via NADPH oxidase, reducing the palmitoylation of receptor-associated Gαi in a JNK-dependent manner. Selective inhibition of PRDX6 blocks Gαi depalmitoylation, prevents the enhanced receptor G-protein association and blocks acute analgesic tolerance to morphine and kappa opioid receptor inactivation in vivo. Opioid stimulation of JNK also inactivates dopamine D2 receptors in a PRDX6-dependent manner. We show that the loss of this lipid modification distorts the receptor G-protein association, thereby preventing agonist-induced guanine nucleotide exchange. These findings establish JNK-dependent PRDX6 recruitment and oxidation-induced Gαi depalmitoylation as an additional mechanism of Gαi-G-protein-coupled receptor inactivation.Opioid receptors are important modulators of nociceptive pain. Here the authors show that opioid receptor activation recruits peroxiredoxin 6 (PRDX6) to the receptor-Gαi complex by c-Jun N-terminal kinase, resulting in Gαi depalmitoylation and enhanced receptor-Gαi association.
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