ArticleThe EMBO journal2005
Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis.
Article in The EMBO journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 138 citations in OpenAlex.
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- Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.Protein & cell · 2025Article
- The relationship mammalian p38 with human health and its homolog Hog1 in response to environmental stresses inFrontiers in cell and developmental biology · 2025Review
- Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development.Molecules (Basel, Switzerland) · 2024Review
- Unveiling the role of host kinases at different steps of influenza A virus life cycle.Journal of virology · 2024Review
- Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control.Cell death & disease · 2024Article
- Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor.International journal of molecular sciences · 2023Review
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- Spoken and Unspoken Matters Regarding the Use of Opioids in Cancer.Journal of pain research · 2022Review
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling.The Journal of cell biology · 2021Article
- Gefitinib induces EGFR and α5β1 integrin co-endocytosis in glioblastoma cells.Cellular and molecular life sciences : CMLS · 2021Article
- Response Mechanisms of Invertebrates toMicrobiology and molecular biology reviews : MMBR · 2021Review
- The Two Sides of the Same Coin-Influenza Virus and Intracellular Signal Transduction.Cold Spring Harbor perspectives in medicine · 2021Review
- The Effects of Low Dose Naltrexone on Opioid Induced Hyperalgesia and Fibromyalgia.Frontiers in psychiatry · 2021Article
- Hypersensitivity of Vps33B mutant flies to non-pathogenic infections is dictated by aberrant activation of p38b MAP kinase.Traffic (Copenhagen, Denmark) · 2020Article
- P38α MAPK Signaling-A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease.International journal of molecular sciences · 2020Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphine analgesic properties and side effects such as tolerance are mediated by the mu opioid receptor (MOR) whose endocytosis is considered of primary importance for opioid pharmacological effects. Here, we show that p38 mitogen-activated protein kinase (MAPK) activation is required for MOR endocytosis and sufficient to trigger its constitutive internalization in the absence of agonist. Further studies established a functional link between p38 MAPK and the small GTPase Rab5, a key regulator of endocytosis. Expression of an activated mutant of Rab5 stimulated endocytosis of MOR ligand-independently in wild-type but not in p38alpha-/- cells. We found that p38alpha can phosphorylate the Rab5 effectors EEA1 and Rabenosyn-5 on Thr-1392 and Ser-215, respectively, and these phosphorylation events regulate the recruitment of EEA1 and Rabenosyn-5 to membranes. Moreover, phosphomimetic mutation of Thr-1392 in EEA1 can bypass the requirement for p38alpha in MOR endocytosis. Our results highlight a novel mechanism whereby p38 MAPK regulates receptor endocytosis under physiological conditions via phosphorylation of Rab5 effectors.
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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.