ArticleThe EMBO journal2002
A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 123 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
123 citing papers in PubMed, 281 citations in OpenAlex.
- Regulation of epidermal growth factor receptors: The role of c-Cbl, Cdc42, and miRNAs in breast cancer.Biochemistry and biophysics reports · 2026Review
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds.Cell communication and signaling : CCS · 2024Article
- The Configuration of GRB2 in Protein Interaction and Signal Transduction.Biomolecules · 2024Review
- Pan-EGFR Inhibitor Dacomitinib Resensitizes Paclitaxel and Induces Apoptosis via Elevating Intracellular ROS Levels in Ovarian Cancer SKOV3-TR Cells.Molecules (Basel, Switzerland) · 2024Article
- The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.Frontiers in physiology · 2024Review
- Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.Molecular biology of the cell · 2023Article
- Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids.PLoS pathogens · 2023Article
- ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection.Life science alliance · 2023Article
- EGFR-Targeted Photodynamic Therapy.Pharmaceutics · 2022Review
- Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases.Frontiers in endocrinology · 2022Review
- Multidimensional Analysis of CHMP Family Members in Hepatocellular Carcinoma.International journal of general medicine · 2022Article
- Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis.Annual review of biochemistry · 2021Review
- Review
- Knockout of c-Cbl slows EGFR endocytic trafficking and enhances EGFR signaling despite incompletely blocking receptor ubiquitylation.Pharmacology research & perspectives · 2021Article
- ZNRF1 Mediates Epidermal Growth Factor Receptor Ubiquitination to Control Receptor Lysosomal Trafficking and Degradation.Frontiers in cell and developmental biology · 2021Article
- The Role of Post-Translational Modifications in Targeting Protein Cargo to Extracellular Vesicles.Sub-cellular biochemistry · 2021Article
- USP25 Regulates EGFR Fate by Modulating EGF-Induced Ubiquitylation Dynamics.Biomolecules · 2020Article
- Recurrent EGFR alterations in NTRK3 fusion negative congenital mesoblastic nephroma.Practical laboratory medicine · 2020Article
- SGCE Promotes Breast Cancer Stem Cells by Stabilizing EGFR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) is controlled by c-Cbl, a ubiquitin ligase that binds multiple signaling proteins, including the Grb2 adaptor. Consistent with a negative role for c-Cbl, here we report that defective Tyr1045 of EGFR, an inducible c-Cbl docking site, enhances the mitogenic response to EGF. Signaling potentiation is due to accelerated recycling of the mutant receptor and a concomitant defect in ligand-induced ubiquitylation and endocytosis of EGFR. Kinetic as well as morphological analyses of the internalization-defective mutant receptor imply that c-Cbl-mediated ubiquitylation sorts EGFR to endocytosis and to subsequent degradation in lysosomes. Unexpectedly, however, the mutant receptor displayed significant residual ligand-induced ubiquitylation, especially in the presence of an overexpressed c-Cbl. The underlying mechanism seems to involve recruitment of a Grb2 c-Cbl complex to Grb2-specific docking sites of EGFR, and concurrent acceleration of receptor ubiquitylation and desensitization. Thus, in addition to its well-characterized role in mediating positive signals, Grb2 can terminate signal transduction by accelerating c-Cbl-dependent sorting of active tyrosine kinases to destruction.
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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.