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J Biol Chem, Vol. 274, Issue 2, 607-617, January 8, 1999

The Role of Tec Protein-tyrosine Kinase in T Cell Signaling

Wen-Chin Yang, Marguerite Ghiotto, Bernadette Barbarat, and Daniel Olive

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.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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