ArticleMolecular biology of the cell2023
Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.
Article in Molecular biology of the cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Ubiquitin-specific protease 11 facilitates the activation and proliferation of renal interstitial fibroblasts through epidermal growth factor receptor signaling pathways.Renal failure · 2026Article
- Regulation of epidermal growth factor receptors: The role of c-Cbl, Cdc42, and miRNAs in breast cancer.Biochemistry and biophysics reports · 2026Review
- An AI-derived peptide PCa2 suppresses pancreatic cancer growth via modulation of the ErbB/PI3K/AKT/mTOR/MYC signaling axis.Cell communication and signaling : CCS · 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
- A c-Cbl/Cbl-b antagonist inhibits EGFR ubiquitylation and sustains EGFR phosphorylation to enhance corneal re-epithelialization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Article
- Secretory carrier membrane protein 3 modulates nuclear ERK1/2 signaling and drug response in triple-negative breast cancer.Frontiers in oncology · 2026Article
- Emergent eukaryotic directional sensing via receptor degradation and diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites.Molecular biology of the cell · 2024Article
- Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation.The Journal of clinical investigation · 2024Article
- FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies.Cancer communications (London, England) · 2024Review
- Crosstalk of growth factor receptors at plasma membrane clathrin-coated sites.bioRxiv : the preprint server for biology · 2024Article
- HER3-targeted therapy: the mechanism of drug resistance and the development of anticancer drugs.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Highly homologous E3 ubiquitin ligases, Cbl and Cbl-b, mediate ubiquitination of EGF receptor (EGFR), leading to its endocytosis and lysosomal degradation. Cbl and Cbl-b, are thought to function in a redundant manner by binding directly to phosphorylated Y1045 (pY1045) of EGFR and indirectly via the Grb2 adaptor. Unexpectedly, we found that inducible expression of Cbl or Cbl-b mutants lacking the E3 ligase activity but fully capable of EGFR binding does not significantly affect EGFR ubiquitination and endocytosis in human oral squamous cell carcinoma (HSC3) cells which endogenously express Cbl-b at a relatively high level. Each endogenous Cbl species remained associated with ligand-activated EGFR in the presence of an overexpressed counterpart species or its mutant, although Cbl-b overexpression partially decreased Cbl association with EGFR. Binding to pY1045 was the preferential mode for Cbl-b:EGFR interaction, whereas Cbl relied mainly on the Grb2-dependent mechanism. Overexpression of the E3-dead mutant of Cbl-b slowed down EGF-induced degradation of active EGFR, while this mutant and a similar mutant of Cbl did not significantly affect MAPK/ERK1/2 activity. EGF-guided chemotaxis migration of HSC3 cells was diminished by overexpression of the E3-dead Cbl-b mutant but was not significantly affected by the E3-dead Cbl mutant. By contrast, the inhibitory effect of the same Cbl mutant on the migration of OSC-19 cells expressing low Cbl-b levels was substantially stronger than that of the Cbl-b mutant. Altogether, our data demonstrate that Cbl and Cbl-b may operate independently through different modes of EGFR binding to jointly control receptor ubiquitination, endocytic trafficking, and signaling.
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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.