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.