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Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk
Open accessAbstract
Itk is a T cell protein tyrosine kinase (PTK) that, along with Btk and Tec, belongs to a family of cytoplasmic PTKs with N-terminal pleckstrin homology domains. Btk plays a critical role in B lymphocyte development. To determine whether Itk has an analogous role in T lymphocytes, we used gene targeting to prepare mice lacking expression of Itk. Such animals had decreased numbers of mature thymocytes, an effect most clearly observed in mice expressing T cell receptor (TCR) transgenes. Mature T cells from Itk-deficient mice had reduced proliferative responses to allogeneic MHC stimulation and to anti-TCR cross-linking, but responded normally to stimulation with phorbol ester plus ionomycin or with IL-2. These results provide genetic evidence that Itk is involved in T cell development and also suggest that Itk has an important role in proximal events in TCR-mediated signaling pathways.
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Cites
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
Li, E., Bestor, T. H., & Jaenisch, R. (1992) · Cell · doi:10.1016/0092-8674(92)90611-f · Cited by 3,984
Cited by
Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J., & Waterfield, M. D. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.615 · Cited by 1,204
Calcium signalling in lymphocyte activation and disease
Feske, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2152 · Cited by 1,043
CD28 and CTLA-4 coreceptor expression and signal transduction
Rudd, C. E., Taylor, A., & Schneider, H. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00770.x · Cited by 898
Chan, T. O., Rittenhouse, S. E., & Tsichlis, P. N. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.965 · Cited by 737
T-Cell Signaling Regulated by the Tec Family Kinase, Itk
Andreotti, A. H., Schwartzberg, P. L., Joseph, R. E., & Berg, L. J. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002287 · Cited by 593
Metadata
- Authors
- Liao, X. C., & Littman, D. R.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1995-12
- Volume
- 3
- Issue
- 6
- Pages
- 757-769
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2041215937
- Cited by
- 315
- References
- 1
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Liao, X. C., & Littman, D. R. (1995). Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Immunity. https://doi.org/10.1016/1074-7613(95)90065-9
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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