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-beta-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 NH2-terminal kinase, p38 and IkappaB kinase. These results indicate that TAK1 plays a critical role in T cell activation by controlling production of IL-2.
Sakurai
Hiroaki
H
Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. hsakurai@ms.toyama-mpu.ac.jp
Singhirunnusorn
Pattama
P
Shimotabira
Emi
E
Chino
Atsushi
A
Suzuki
Shunsuke
S
Koizumi
Keiichi
K
Saiki
Ikuo
I
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001665:Binding Sites; D018106:CD28 Antigens; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional; D013601:T-Lymphocytes / Q000378:metabolism*; D018808:Transcription Factor AP-1; D015533:Transcriptional Activation; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D007376:Interleukin-2; D020930:MAP Kinase Kinase Kinases; D018808:Transcription Factor AP-1; D000099151:MAP Kinase Kinase Kinase 7; C486300:TAB1 protein, human