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J Biol Chem, Vol. 274, Issue 2, 607-617, January 8, 1999
From INSERM U119, 27 Boulevard Lei Roure,
13009 Marseille, France
The Tec protein-tyrosine kinase family includes
Btk, Itk/Tsk/Emt, Tec, Rlk/Txk, and Bmx which are involved in signals
mediated by various cytokines or antigen receptors. Itk is expressed
primarily in T cells and activated by TCR/CD3, CD28, and CD2. However,
the defect in T cell signaling in itk-deficient mice is
very modest. Thus, we looked for other Tec family kinases that could be
expressed in lymphoid cells and involved in T cell signal transduction. Here, we demonstrate that Tec, expressed in T cells, is activated following TCR/CD3 or CD28 ligation and interacts with CD28 receptor in
an activation-dependent manner. This interaction involves
the Tec SH3 domain and the proline-rich motifs in CD28. We also show that Tec can phosphorylate p62dok, one CD28-specific substrate,
whereas Itk cannot. Overexpression of Tec but not Itk can enhance the
interleukin-2 promoter activity mediated by TCR/CD3 or CD28 stimulation
and introduction of a kinase-dead Tec but not Itk can suppress
interleukin-2 expression, indicating that Tec is directly involved in T
cell activation. Altogether, these data demonstrate that Tec kinase is
an integral component of T cell signaling and that the two Tec family
kinases, Tec and Itk, have distinct roles in T cell activation.
The Role of Tec Protein-tyrosine Kinase in T Cell Signaling
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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