Tec kinase is involved in transcriptional regulation of IL-2 and IL-4 in the CD28 pathway.
The Tec protein tyrosine kinase (PTK) family includes Btk, Itk/Tsk/Emt, Tec, Rlk/Txk and Bmx, which are involved in signals mediated by various surface receptors. We have previously found (W.-C. Yang et al., J. Biol. Chem. 1999. 274: 607) that Tec is involved in T cell signaling in a way distinct from Itk. However, little is known about the role of Tec in regulation of cytokine expression in the CD28 pathway. Here, we show in heterologous COS-7 cells that co-expression of Src family kinases such as Lck increases Tec activation or CD28-mediated Tec activation, whereas co-expression of kinase-dead Lck blocks Tec activation or CD28-mediated Tec activation. These data suggest that CD28 activates Tec via Src family PTK. As is the case for the IL-2 promoter, transcription of the IL-4 promoter is enhanced by overexpression of wild-type Tec but inhibited by overexpression of a kinase-dead version of Tec following CD28 activation. These results imply that Tec can modulate transcription of Th1 and Th2 cytokines in a kinase-dependent manner. Consistent with the hypothesis postulated above that Lck can regulate Tec activation, overexpression of kinase-dead Lck can block Tec-induced cytokine expression following CD28 ligation.
Yang
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INSERM U119, Marseille, France.
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D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism*; D019556:COS Cells; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology; D015533:Transcriptional Activation
D018106:CD28 Antigens; D007376:Interleukin-2; D015847:Interleukin-4; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)