Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk.
Tyrosine protein phosphorylation is necessary for antigen receptor-mediated activation of T lymphocytes. 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 residue. 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 spleen. 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.
McGill Cancer Centre, McGill University, Montreal, Canada.
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Chow
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Fournel
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Davidson
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Veillette
D000818:Animals; D001483:Base Sequence; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human