ArticleThe Journal of experimental medicine2000
Tec family kinases modulate thresholds for thymocyte development and selection.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 130 citations in OpenAlex.
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
- Article
- TCR/ITK Signaling in Type 1 Regulatory T cells.Advances in experimental medicine and biology · 2021Article
- Kinase inhibition in autoimmunity and inflammation.Nature reviews. Drug discovery · 2021Review
- Thymic regulatory T cells arise via two distinct developmental programs.Nature immunology · 2019Article
- Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses.Frontiers in immunology · 2019Review
- Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development.European journal of immunology · 2017Article
- Phenotype of NK-Like CD8(+) T Cells with Innate Features in Humans and Their Relevance in Cancer Diseases.Frontiers in immunology · 2017Article
- A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Allele-sensitive mutant, Itkas, reveals that Itk kinase activity is required for Th1, Th2, Th17, and iNKT-cell cytokine production.European journal of immunology · 2015Article
- The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation.Journal of leukocyte biology · 2015Review
- Immunodeficiency and immune dysregulation associated with proximal defects of T cell receptor signaling.Current opinion in immunology · 2014Review
- SAP-Dependent and -Independent Regulation of Innate T Cell Development Involving SLAMF Receptors.Frontiers in immunology · 2014Article
- TGF-β conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA.Mucosal immunology · 2013Article
- Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells requires stronger T-cell receptor signals than conventional CD4 T cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Selection of self-reactive T cells in the thymus.Annual review of immunology · 2012Review
- TEC and MAPK Kinase Signalling Pathways in T helper (TJournal of clinical & cellular immunology · 2012Article
- Impairment of immunological synapse formation in adaptively tolerant T cells.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates.The FEBS journal · 2011Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tec family kinases are implicated in T cell receptor (TCR) signaling, and combined mutation of inducible T cell kinase (Itk) and resting lymphocyte kinase (Rlk)/Txk in mice dramatically impairs mature T cell function. Nonetheless, mutation of these kinases still permits T cell development. While itk(-)(/)- mice exhibit mild reductions in T cells with decreased CD4/CD8 cell ratios, rlk(-)(/)-itk(-)(/)- mice have improved total T cell numbers yet maintain decreased CD4/CD8 ratios. Using TCR transgenics and an in vitro thymocyte deletion model, we demonstrate that mutation of Tec kinases causes graded defects in thymocyte selection, leading to a switch from negative to positive selection in rlk(-)(/)-itk(-)(/)- animals. The reduction in both positive and negative selection and decreased CD4/CD8 ratios correlates with decreased biochemical parameters of TCR signaling, specifically defects in capacitive Ca(2+) influx and activation of the mitogen-activated kinases extracellular signal-regulated kinase 1 and 2. Thus, Tec kinases influence cell fate determination by modulating TCR signaling, leading to altered thresholds for thymocyte selection. These results provide support for a quantitative model for thymic development and provide evidence that defects in negative selection can substantially alter thymic cellularity.
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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.