Abstract
Productive interaction of a T lymphocyte with an antigen-presenting cell results in the clustering of the T-cell antigen receptor (TCR) and the recruitment of a large signalling complex to the site of cell–cell contact1,2. Subsequent signal transduction resulting in cytokine gene expression requires the activation of one or more of the multiple isoenzymes of serine/threonine-specific protein kinase C (PKC)3. Among the several PKC isoenzymes expressed in T cells, PKC-θ is unique in being rapidly recruited to the site of TCR clustering4. Here we show that PKC-θ is essential for TCR-mediated T-cell activation, but is dispensable during TCR-dependent thymocyte development. TCR-initiated NF-κB activation was absent from PKC-θ-/- mature T lymphocytes, but was intact in thymocytes. Activation of NF-κB by tumour-necrosis factor α and interleukin-1 was unaffected in the mutant mice. Although studies in T-cell lines had suggested that PKC-θ regulates activation of the JNK signalling pathway5,6, induction of JNK was normal in T cells from mutant mice. These results indicate that PKC-θ functions in a unique pathway that links the TCR signalling complex to the activation of NF-κB in mature T lymphocytes.
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Acknowledgements
We thank S. Marmon for preparing fusion proteins used to generate antisera; M. Brown for analysis of the antisera; B. Alfonso and W. O'Brien for genotyping; D. Alpert, M. Rincon and R. Davis for advice on the JNK assays; and E. Skolnik, A. Zychlinsky, Y. Zou and D. Unutmaz for their critical reading of the manuscript. C.W.A. is supported by a fellowship award from the Medical Research Council of Canada. Z.S. is supported by an NIH Molecular Oncology and Immunology training grant. E.M.S. is a Howard Hughes Medical Institute–NIH Research Scholar. P.L.S. is supported in part by a Searle Scholar award, and A.K is supported by a grant from the NIH. W.E. is an Associate and D.R.L. is an Investigator of the Howard Hughes Medical Institute.
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Sun, Z., Arendt, C., Ellmeier, W. et al. PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes. Nature 404, 402–407 (2000). https://doi.org/10.1038/35006090
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DOI: https://doi.org/10.1038/35006090
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