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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Sakurai H,Singhirunnusorn P,Shimotabira E,Chino A,Suzuki S,Koizumi K,Saiki I

doi

10.1016/j.febslet.2005.10.059

keywords:

subject

Has Abstract

pub_date

2005-12-05 00:00:00

pages

6641-6

issue

29

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)01332-3

journal_volume

579

pub_type

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