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TAK1‐mediated transcriptional activation of CD28‐responsive element and AP‐1‐binding site within the IL‐2 promoter in Jurkat T cells
Author(s) -
Sakurai Hiroaki,
Singhirunnusorn Pattama,
Shimotabira Emi,
Chino Atsushi,
Suzuki Shunsuke,
Koizumi Keiichi,
Saiki Ikuo
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.059
Subject(s) - jurkat cells , cd28 , kinase , activator (genetics) , microbiology and biotechnology , chemistry , transcription factor , map kinase kinase kinase , p38 mitogen activated protein kinases , protein kinase c , protein kinase a , t cell , biology , in vitro , receptor , biochemistry , gene , cytotoxic t cell , immunology , immune system
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.