Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex

J Biol Chem. 2001 Jul 6;276(27):25378-85. doi: 10.1074/jbc.M011363200. Epub 2001 May 10.

Abstract

Jak3 is responsible for growth signals by various cytokines such as interleukin (IL)-2, IL-4, and IL-7 through association with the common gamma chain (gammac) in lymphocytes. We found that T cells from Jak3-deficient mice exhibit impairment of not only cytokine signaling but also early activation signals and that Jak3 is phosphorylated upon T cell receptor (TCR) stimulation. TCR-mediated phosphorylation of Jak3 is independent of IL-2 receptor/gammac but is dependent on Lck and ZAP-70. Jak3 was found to be assembled with the TCR complex, particularly through direct association with CD3zeta via its JH4 region, which is a different region from that for gammac association. These results suggest that Jak3 plays a role not only in cell growth but also in T cell activation and represents cross-talk of a signaling molecule between TCR and growth signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • Calcium / metabolism
  • Cytokines / metabolism*
  • Enzyme Activation
  • Humans
  • Janus Kinase 3
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Mice
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Rabbits
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Interleukin-2 / metabolism
  • Spleen / cytology
  • T-Lymphocytes / enzymology
  • Transfection
  • Tumor Cells, Cultured
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • Cytokines
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Protein-Tyrosine Kinases
  • JAK3 protein, human
  • Jak3 protein, mouse
  • Janus Kinase 3
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • Zap70 protein, mouse
  • Calcium