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Signal transduction by MAP kinases in T lymphocytes

Oncogene volume 20, pages 2490–2497 (2001)Cite this article

Mitogen-activated protein (MAP) kinases have been implicated in many physiological processes, including cell proliferation, differentiation, and death. These processes are relevant to the development and function of T cells. Here we will review recent progress that has established roles for MAP kinases in T cell development and function.

The ERK, p38, and JNK groups of MAP kinases are present in T cells. These protein kinases are activated by the same protein kinase cascades that lead to MAP kinase activation in other cell types. However, the mechanisms that activate these MAP kinase cascades are distinctive in T cells. For example, activation of the T cell receptor (TcR) can cause increased ERK activation, while co-stimulation by accessory molecules (e.g. CD28) is required for JNK activation (Su et al., 1994). It remains unclear how upstream signals triggered by the TcR modulate the MAP kinase signaling pathways. Although a role for calcineurin and protein kinase C theta has also been proposed (Werlen et al., 1998), more recent studies have shown that protein kinase C theta is not required for JNK activation in T cells (Sun et al., 2000). It is therefore unclear how CD28-mediated signals integrate with TcR-mediated signals to control activation of the MAP kinase pathways. However, signal integration may involve co-operation between Syk and Rac (Jacinto et al., 1998). Indeed, gene disruption studies demonstrate that the Rac2 gene is required for activation of JNK and p38 MAP kinase (Li et al., 2000).

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Acknowledgements

We thank Dr EF Wagner for sharing results prior to publication. RJ Davis and RA Flavell are investigators of the Howard Hughes Medical Institute. Studies performed in our laboratories were supported, in part, by grants from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Medicine, Immunobiology Program, University of Vermont, Burlington, 05405, Vermont, VT, USA

    Mercedes Rincón

  2. Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, 06520, Connecticut CT, USA

    Richard A Flavell

  3. Department of Biochemistry & Molecular Biology, Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachussetts Medical School, Worcester, 01605, Massachusetts, MA, USA

    Roger J Davis

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Rincón, M., Flavell, R. & Davis, R. Signal transduction by MAP kinases in T lymphocytes. Oncogene 20, 2490–2497 (2001). https://doi.org/10.1038/sj.onc.1204382

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