TAK1-mediated transcriptional activation of CD28-responsive element and AP-1-binding site within the IL-2 promoter in Jurkat T cells

We focused on the functional involvement of transforming growth factor-β-activated kinase 1 (TAK1) in transcriptional regulation of interleukin-2 (IL-2) in T cells. Costimulation of Jurkat cells with 12- O-tetradecanoylphorbol-13-acetate and A23187 leads to a rapid phosphorylation of TAK1 and TAK1-binding protein 1 (TAB1), critical for TAK1 activation. A specific inhibitor of TAK1 blocked production of IL-2. In addition, overexpression of TAK1 and TAB1 induced secretion of IL-2. CD28-responsive element/activator protein-1-binding site (RE/AP) within the IL-2 promoter was a functional target for TAK1. The RE/AP-driven transcription was regulated by TAK1-mediated activation of the c-Jun NH 2-terminal kinase, p38 and IκB kinase. These results indicate that TAK1 plays a critical role in T cell activation by controlling production of IL-2.