Rac1 and PAK1 are upstream of IKK-ε and TBK-1 in the viral activation of interferon regulatory factor-3

被引：104

作者：

Ehrhardt, C

Kardinal, C

Wurzer, WJ

Wolff, T

von Eichel-Streiber, C

Pleschka, S

Planz, O

Ludwig, S

机构：

[1] Univ Dusseldorf, Inst Mol Med IMM, D-40225 Dusseldorf, Germany

[2] Univ Wurzburg, Inst Med Strahlenkunde & Zellforsch, D-97078 Wurzburg, Germany

[3] Med Hochsch, Dept Pediat Hematol & Oncol, D-30626 Hannover, Germany

[4] Robert Koch Inst, D-13353 Berlin, Germany

[5] Univ Mainz, Inst Med Microbiol, D-55101 Mainz, Germany

[6] Univ Giessen, Inst Med Virol, D-35392 Giessen, Germany

[7] BFAV, Inst Immunol, D-72076 Tubingen, Germany

来源：

FEBS LETTERS | 2004年 / 567卷 / 2-3期

关键词：

viral infection; transcription factor; signal transduction; rho GTPase; anti-viral response;

D O I：

10.1016/j.febslet.2004.04.069

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The anti-viral type I interferon (IFN) response is initiated by the immediate induction of IFNbeta, which is mainly controlled by the IFN-regulatory factor-3 (IRF-3). The signaling pathways mediating viral IRF-3 activation are only poorly defined. We show that the Rho GTPase Rac1 is activated upon virus infection and controls IRF-3 phosphorylation and activity. Inhibition of Rac1 leads to reduced IFNbeta promoter activity and to enhanced virus production. As a downstream mediator of Rac signaling towards IRF-3, we have identified the kinase p21-activated kinase (PAK1). Furthermore, both Rac1 and PAK1 regulate the recently described IRF-3 activators, IkappaB kinase-V and TANK-binding kinase-1, establishing a first canonical virus-induced IRF-3 activating pathway. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：230 / 238

页数：9

共 35 条

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