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Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk

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Abstract

TYROSINE protein phosphorylation is necessary for antigen receptor-mediated activation of T lymphocytes1. This signal is generated at least in part by the Src-related tyrosine protein kinases p56lck and p59fynT (refs 2, 3). The activity of these two enzymes is repressed by phosphorylation of a conserved carboxy-terminal tyrosine residue2,3. Recent studies suggest that this inhibitory phosphorylation may be caused by p50csk (for C-terminal Src kinase), a tyrosine protein kinase which accumulates most abundantly in thymus and spleen4–8. To investigate the function of Csk in T lymphocytes and characterize the processes regulating T-cell receptor (TCR) signalling, we examined the effects of overexpression of Csk on the physiology of an antigen-specific mouse T-cell line. We report here that p50csk negatively regulates TCR-induced tyrosine protein phosphorylation and lymphokine production. This provides evidence for the involvement of Csk in the regulation of T-cell activation.

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Authors and Affiliations

  1. McGill Cancer Centre, McGill University, Montreal, H3G 1Y6, Canada

    Lionel M. L. Chow, Marielle Fournel, Dominique Davidson & André Veillette

  2. Department of Biochemistry, McGill University, Montreal, H3G 1Y6, Canada

    Lionel M. L. Chow & André Veillette

  3. Department of Medicine, McGill University, Montreal, H3G 1Y6, Canada

    André Veillette

  4. Department of Oncology, McGill University, Montreal, H3G 1Y6, Canada

    André Veillette

  5. Division of Medical Oncology, Department of Medicine, Montreal General Hospital, Montreal, H3G 1A4, Canada

    André Veillette

Authors
  1. Lionel M. L. Chow
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  2. Marielle Fournel
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  3. Dominique Davidson
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  4. André Veillette
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Chow, L., Fournel, M., Davidson, D. et al. Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk. Nature 365, 156–160 (1993). https://doi.org/10.1038/365156a0

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