ArticleSignal transduction2002
An essential role of ubiquitination in Cbl-mediated negative regulation of the Src-family kinase Fyn.
Article in Signal transduction, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 23 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
- Fyn Kinase: A Potential Target in Glucolipid Metabolism and Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Analysis of hepatitis B virus integration identifies KMT2B as a novel cancer-related gene in pancreatic cancer.Clinical and translational medicine · 2025Article
- USP8-Dependent Family Tyrosine Kinase Promotes the Malignant Progression of Esophageal Squamous Cell Carcinoma by Upregulating Protein Tyrosine Kinase 2 Expression.Thoracic cancer · 2025Article
- The ubiquitin ligases Cbl and Cbl-b regulate macrophage growth by controlling CSF-1R import into macropinosomes.Molecular biology of the cell · 2024Article
- FYN: emerging biological roles and potential therapeutic targets in cancer.Journal of translational medicine · 2023Review
- Alzheimer's disease: insights from a network medicine perspective.Scientific reports · 2022Article
- Depletion of Csk preferentially reduces the protein level of LynA in a Cbl-dependent manner in cancer cells.Scientific reports · 2020Article
- Article
- Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases.Biochimica et biophysica acta · 2013Review
- Oncogenic Signaling by Leukemia-Associated Mutant Cbl Proteins.Biochemistry and analytical biochemistry : current research · 2012Article
- Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75).Cellular and molecular life sciences : CMLS · 2011Article
- A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in Toll/IL-1R-induced inflammatory signaling.Molecular and cellular biology · 2005Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Cbl family of ubiquitin ligases function as negative regulators of activated receptor tyrosine kinases by facilitating their ubiquitination and subsequent lysosomal targeting. Here, we have investigated the role of Cbl ubiquitin ligase activity in the negative regulation of a non-receptor tyrosine kinase, the Src-family kinase Fyn. Using primary embryonic fibroblasts from Cbl(+/+) and Cbl(-/-) mice, we demonstrate that endogenous Cbl mediates the ubiquitination of Fyn and dictates the rate of Fyn turnover. By analyzing CHO-TS20 cells with a temperature-sensitive ubiquitin activating enzyme, we demonstrate that intact cellular ubiquitin machinery is required for Cbl-induced degradation of Fyn. Analyses of Cbl mutants, with mutations in or near the RING finger domain, in 293T cells revealed that the ubiquitin ligase activity of Cbl is essential for Cbl-induced degradation of Fyn by the proteasome pathway. Finally, use of a SRE-luciferase reporter demonstrated that Cbl-dependent negative regulation of Fyn function requires the region of Cbl that mediates the ubiquitin ligase activity. Given the conservation of structure between various Src-family kinases and the ability of Cbl to interact with multiple members of this family, Cbl-dependent ubiquitination could serve a general role to negatively regulate activated Src-family kinases.
Identifiers
19966925PMC2788922W2080304783What OpenQuestion holds
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.