ArticleThe Journal of experimental medicine2003
A mouse with a loss-of-function mutation in the c-Cbl TKB domain shows perturbed thymocyte signaling without enhancing the activity of the ZAP-70 tyrosine kinase.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants.Human genomics · 2022Article
- Feedback regulation of RTK signaling in development.Developmental biology · 2019Review
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- ModelingBlood · 2017Article
- Regulation of T cell development by c-Cbl: essential role of Lck.International immunology · 2015Article
- Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.Bone · 2014Article
- Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases.Biochimica et biophysica acta · 2013Review
- Article
- Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling: Insights from in vivo models.Communicative & integrative biology · 2011Article
- 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
- ZAP-70: an essential kinase in T-cell signaling.Cold Spring Harbor perspectives in biology · 2010Review
- Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development.The EMBO journal · 2010Article
- c-Cbl promotes T cell receptor-induced thymocyte apoptosis by activating the phosphatidylinositol 3-kinase/Akt pathway.The Journal of biological chemistry · 2010Article
- Organization of proximal signal initiation at the TCR:CD3 complex.Immunological reviews · 2009Review
- c-Cbl tyrosine kinase-binding domain mutant G306E abolishes the interaction of c-Cbl with CD38 and fails to promote retinoic acid-induced cell differentiation and G0 arrest.The Journal of biological chemistry · 2009Article
- Lymphocyte signaling: beyond knockouts.Nature immunology · 2009Review
- Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Alpha-MSH regulates protein ubiquitination in T cells.Cellular and molecular biology (Noisy-le-Grand, France) · 2006Article
- Loss of c-Cbl RING finger function results in high-intensity TCR signaling and thymic deletion.The EMBO journal · 2005Article
- c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses.The Biochemical journal · 2005Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unique tyrosine kinase binding (TKB) domain of Cbl targets phosphorylated tyrosines on activated protein tyrosine kinases (PTKs); this targeting is considered essential for Cbl proteins to negatively regulate PTKs. Here, a loss-of-function mutation (G304E) in the c-Cbl TKB domain, first identified in Caenorhabditis elegans, was introduced into a mouse and its effects in thymocytes and T cells were studied. In marked contrast to the c-Cbl knockout mouse, we found no evidence of enhanced activity of the ZAP-70 PTK in thymocytes from the TKB domain mutant mouse. This finding contradicts the accepted mechanism of c-Cbl-mediated negative regulation, which requires TKB domain targeting of phosphotyrosine 292 in ZAP-70. However, the TKB domain mutant mouse does show aspects of enhanced signaling that parallel those of the c-Cbl knockout mouse, but these involve the constitutive activation of Rac and not enhanced PTK activity. Furthermore, the enhanced signaling in CD4(+)CD8(+) double positive thymocytes appears to be compensated by the selective down-regulation of CD3 on mature thymocytes and peripheral T cells from both strains of mutant c-Cbl mice.
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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.