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

Nature. 1993 Sep 9;365(6442):156-60. doi: 10.1038/365156a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CSK Tyrosine-Protein Kinase
  • Cell Line
  • Cloning, Molecular
  • DNA
  • Humans
  • Interleukin-2 / biosynthesis
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / physiology*
  • Rats
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • Tyrosine / metabolism
  • src-Family Kinases*


  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Tyrosine
  • DNA
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human