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Enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine protein kinase p56lck

Nature volume 350, pages 62–66 (1991)Cite this article

Abstract

LYMPHOCYTE-specific tyrosine protein kinase p56lck is physically associated with CD4 and CDS T-cell surface molecules, suggesting that it may transduce CD4/CD8-triggered tyrosine phosphorylation signals during antigen stimulation1,2. Indeed, antibody-mediated aggregation of CD4 (to mimic interaction with its ligand, major histocompatibility complex (MHC) class II molecules), rapidly elevates the kinase activity of p56lck (refs 3, 4) and is associated with marked changes in tyrosine protein phosphorylation4-6. Genetic analyses suggest that the interaction of CD4/CD8 with p56lck results in a positive signal during antigen-induced T-cell activation7-10. To evaluate directly the role of p56lck in T-cell activation, we introduced a constitutively activated form of Lck protein (tyrosine 505 to phenylalanine 505 mutant; refs 11-13) in a CD4-negative, MHC-class II restricted mouse T-cell hybridoma14. We report here that, as for transfection of CD410,15,16, expression of the Lck mutant enhanced T-lymphocyte responsiveness. This finding provides direct evidence that p56lck can positively regulate T-cell functions and that it mediates at least some of the effects of CD4 and CDS on T-cell activation.

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Author notes

  1. André Veillette: To whom correspondence should be addressed.

Authors and Affiliations

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

    Ninan Abraham & André Veillette

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

    André Veillette

  3. Division of Immunology and Rheumatology, Department of Medicine, Stanford University Medical Center, Stanford, California, 94305, USA

    M. Carrie Miceli & Jane R. Parnes

Authors
  1. Ninan Abraham
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  2. M. Carrie Miceli
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  3. Jane R. Parnes
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  4. André Veillette
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Abraham, N., Miceli, M., Parnes, J. et al. Enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine protein kinase p56lck. Nature 350, 62–66 (1991). https://doi.org/10.1038/350062a0

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