ArticleThe Journal of experimental medicine1997
Itk negatively regulates induction of T cell proliferation by CD28 costimulation.
Article in The Journal of experimental medicine, 1997. 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, 52 citations in OpenAlex.
- Ibrutinib treatment improves T cell number and function in CLL patients.The Journal of clinical investigation · 2017Trial
- PKC-theta-mediated signal delivery from the TCR/CD28 surface receptors.Frontiers in immunology · 2012Article
- Itk: the rheostat of the T cell response.Journal of signal transduction · 2011Article
- FK506 causes cellular and functional defects in human natural killer cells.Journal of leukocyte biology · 2010Article
- Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells.BMC genomics · 2009Article
- A role for the Tec family kinase ITK in regulating SEB-induced interleukin-2 production in vivo via c-jun phosphorylation.BMC immunology · 2005Article
- Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP.Current biology : CB · 2003Article
- An important role of CDK inhibitor p18(INK4c) in modulating antigen receptor-mediated T cell proliferation.Journal of immunology (Baltimore, Md. : 1950) · 2001Article
- Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk.The Journal of experimental medicine · 2000Article
- RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.The Journal of experimental medicine · 1999Article
- A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection.The Journal of experimental medicine · 1999Article
- CD28/CTLA-4 and CD80/CD86 families: signaling and function.Immunologic research · 1999Review
- Functional analysis of the T-cell-restricted protein tyrosine kinase Txk.The Biochemical journal · 1998Article
- Efficient CD28 signalling leads to increases in the kinase activities of the TEC family tyrosine kinase EMT/ITK/TSK and the SRC family tyrosine kinase LCK.The Biochemical journal · 1998Article
- Antiviral immune responses in Itk-deficient mice.Journal of virology · 1997Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
CD28 is a cell surface molecule that mediates a costimulatory signal crucial for T cell proliferation and lymphokine production. The signal transduction mechanisms of CD28 are not well understood. Itk, a nonreceptor protein tyrosine kinase specifically expressed in T cells and mast cells, has been implicated in the CD28 signaling pathway because of reports that it becomes phosphorylated on tyrosines and associates with CD28 upon cross-linking of the cell surface molecule. To determine whether Itk plays a functional role in CD28 signaling, we compared T cells from Itk-deficient mice and control mice for their responses to CD28 costimulation. T cells defective in Itk were found to be fully competent to respond to costimulation. Whereas the CD3-mediated proliferative response was severely compromised in the absence of Itk, the calcineurin-independent CD28-mediated response was significantly elevated when compared with cells from control animals. The augmented proliferation was not due to increased production of interleukin-2. The results suggest that Itk has distinct roles in the CD3 versus the CD28 signaling pathways. By negatively regulating the amplitude of signaling upon CD28 costimulation, Itk may provide a means for modulating the outcome of T cell activation during development and during antigen-driven immune responses.
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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.