ArticleThe Journal of biological chemistry2010
c-Cbl promotes T cell receptor-induced thymocyte apoptosis by activating the phosphatidylinositol 3-kinase/Akt pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- SIRT2-mediated deacetylation of LCK governs the magnitude of T cell receptor signaling.Nature immunology · 2026Article
- Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants.Human genomics · 2022Article
- PI3Kδ Forms Distinct Multiprotein Complexes at the TCR Signalosome in Naïve and Differentiated CD4Frontiers in immunology · 2021Article
- CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Targeting Cdc20 as a novel cancer therapeutic strategy.Pharmacology & therapeutics · 2015Review
- Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in the shikonin-induced apoptosis of lung cancer cellsExperimental and therapeutic medicine · 2015Article
- Ubiquitylation as a Rheostat for TCR Signaling: From Targeted Approaches Toward Global Profiling.Frontiers in immunology · 2015Review
- Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.Bone · 2014Article
- APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction.Developmental cell · 2014Article
- Ubiquitin ligase Cbl-b is involved in icotinib (BPI-2009H)-induced apoptosis and G1 phase arrest of EGFR mutation-positive non-small-cell lung cancer.BioMed research international · 2013Article
- Abrogation of Cbl-PI3K interaction increases bone formation and osteoblast proliferation.Calcified tissue international · 2011Article
- RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis.Nature reviews. Cancer · 2011Review
- Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling: Insights from in vivo models.Communicative & integrative biology · 2011Article
- The loss of Cbl-phosphatidylinositol 3-kinase interaction perturbs RANKL-mediated signaling, inhibiting bone resorption and promoting osteoclast survival.The Journal of biological chemistry · 2010Article
- Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in hematopoietic stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of thymocytes to assess T cell receptor (TCR) signaling strength and initiate the appropriate downstream response is crucial for determining their fate. We have previously shown that a c-Cbl RING finger mutant knock-in mouse, in which the E3 ubiquitin ligase activity of c-Cbl is inactivated, is highly sensitive to TCR-induced death signals that cause thymic deletion. This high intensity signal involves the enhanced tyrosine phosphorylation of the mutant c-Cbl protein promoting a marked increase in the activation of Akt. Here we show that this high intensity signal in c-Cbl RING finger mutant thymocytes also promotes the enhanced induction of two mediators of TCR-directed thymocyte apoptosis, Nur77 and the pro-apoptotic Bcl-2 family member, Bim. In contrast, a knock-in mouse harboring a mutation at Tyr-737, the site in c-Cbl that activates phosphatidylinositol 3-kinase, shows reduced TCR-mediated responses including suppression of Akt activation, a reduced induction of Nur77 and Bim, and greater resistance to thymocyte death. These findings identify tyrosine-phosphorylated c-Cbl as a critical sensor of TCR signal strength that regulates the engagement of death-promoting signals.
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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 OpenQuestion graph.