The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT

J Immunol. 1996 Apr 15;156(8):2716-22.

Abstract

Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • CD28 Antigens / physiology
  • Cross-Linking Reagents
  • Drug Synergism
  • Enzyme Activation / immunology
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Lymphoma, T-Cell / enzymology
  • Lymphoma, T-Cell / immunology
  • Phosphorylation
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / immunology*
  • T-Lymphocytes / enzymology*
  • Tumor Cells, Cultured
  • src-Family Kinases / metabolism
  • src-Family Kinases / physiology*

Substances

  • Antibodies, Monoclonal
  • CD28 Antigens
  • Cross-Linking Reagents
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • emt protein-tyrosine kinase
  • src-Family Kinases