A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection

J Exp Med. 1999 Nov 15;190(10):1427-38. doi: 10.1084/jem.190.10.1427.

Abstract

Recent data indicate that several members of the Tec family of protein tyrosine kinases function in antigen receptor signal transduction. Txk, a Tec family protein tyrosine kinase, is expressed in both immature and mature T cells and in mast cells. By overexpressing Txk in T cells throughout development, we found that Txk specifically augments the phospholipase C (PLC)-gamma1-mediated calcium signal transduction pathway upon T cell antigen receptor (TCR) engagement. Although Txk is structurally different from inducible T cell kinase (Itk), another Tec family member expressed in T cells, expression of the Txk transgene could partially rescue defects in positive selection and signaling in itk(-)(/)(-) mice. Conversely, in the itk(+/+) (wild-type) background, overexpression of Txk inhibited positive selection of TCR transgenic thymocytes, presumably due to induction of cell death. These results identify a role for Txk in TCR signal transduction, T cell development, and selection and suggest that the Tec family kinases Itk and Txk perform analogous functions.

MeSH terms

  • Animals
  • Calcium Signaling
  • Cells, Cultured
  • Leukocyte Common Antigens / physiology
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, T-Cell, alpha-beta / physiology
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Tec protein-tyrosine kinase
  • Protein-Tyrosine Kinases
  • Leukocyte Common Antigens