ArticleThe Journal of cell biology2021
Mechanism of p38 MAPK-induced EGFR endocytosis and its crosstalk with ligand-induced pathways.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Synergistic effects and molecular mechanisms of pirfenidone combined with EGFR-TKIs in non-small cell lung cancer.Translational lung cancer research · 2026Article
- Type 2 Diabetes-Induced Molecular and Functional Impairment of Adipose Tissue-Derived Mesenchymal Stromal Cells (ASCs) and Interferon Gamma Priming for Enhanced Diabetic ASC-Based Therapy.Stem cell reviews and reports · 2026Article
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Endolysosomal two-pore channels regulate a conserved entry pathway for enteroviruses.The Journal of general virology · 2026Article
- Small-molecule CBLB inhibitor abolishes EGFR ubiquitination, reduces receptor endocytosis, and diminishes cell motility signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Small-molecule CBLB inhibitor abolishes EGFR ubiquitination, reduces receptor endocytosis and diminishes cell motility signaling.bioRxiv : the preprint server for biology · 2026Article
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Enhanced HER2 internalization by clathrin-dependent endocytosis in non-small cell lung cancer positive for HER2 mutations.British journal of cancer · 2025Article
- SRC and ERK Regulate the Turnover of Cytoskeletal Keratin Filaments.International journal of molecular sciences · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Modular Nanotransporters Deliver Anti-Keap1 Monobody into Mouse Hepatocytes, Thereby Inhibiting Production of Reactive Oxygen Species.Pharmaceutics · 2024Article
- Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.Molecular biology of the cell · 2023Article
- Loss of EGF receptor polarity enables homeostatic imbalance in epithelial-cell models.Molecular biology of the cell · 2023Article
- Piezo1 activates noncanonical EGFR endocytosis and signaling.Science advances · 2023Article
- Titanium particles inhibit bone marrow mesenchymal stem cell osteogenic differentiation through the MAPK signaling pathway.FEBS open bio · 2023Article
- Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR.Histochemistry and cell biology · 2023Article
- Magnetofection of miR-21 promoted by electromagnetic field and iron oxide nanoparticles via the p38 MAPK pathway contributes to osteogenesis and angiogenesis for intervertebral fusion.Journal of nanobiotechnology · 2023Article
- Targeted Quantification of Protein Phosphorylation and Its Contributions towards Mathematical Modeling of Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- Porcine epidemic diarrhea virus causes diarrhea by activating EGFR to regulates NHE3 activity and mobility on plasma membrane.Frontiers in microbiology · 2023Article
- Small molecules targeting endocytic uptake and recycling pathways.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Ligand binding triggers clathrin-mediated and, at high ligand concentrations, clathrin-independent endocytosis of EGFR. Clathrin-mediated endocytosis (CME) of EGFR is also induced by stimuli activating p38 MAPK. Mechanisms of both ligand- and p38-induced endocytosis are not fully understood, and how these pathways intermingle when concurrently activated remains unknown. Here we dissect the mechanisms of p38-induced endocytosis using a pH-sensitive model of endogenous EGFR, which is extracellularly tagged with a fluorogen-activating protein, and propose a unifying model of the crosstalk between multiple EGFR endocytosis pathways. We found that a new locus of p38-dependent phosphorylation in EGFR is essential for the receptor dileucine motif interaction with the σ2 subunit of clathrin adaptor AP2 and concomitant receptor internalization. p38-dependent endocytosis of EGFR induced by cytokines was additive to CME induced by picomolar EGF concentrations but constrained to internalizing ligand-free EGFRs due to Grb2 recruitment by ligand-activated EGFRs. Nanomolar EGF concentrations rerouted EGFR from CME to clathrin-independent endocytosis, primarily by diminishing p38-dependent endocytosis.
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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.