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- Title
Rac1 and PAK1 are upstream of IKK-#x03B5; and TBK-1 in the viral activation of interferon regulatory factor-3
- Authors
Ehrhardt, Christina; Kardinal, Christian; Wurzer, Walter J.; Wolff, Thorsten; von Eichel-Streiber, Christoph; Pleschka, Stephan; Planz, Oliver; Ludwig, Stephan
- Abstract
The anti-viral type I interferon (IFN) response is initiated by the immediate induction of IFNβ, 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 IFNβ 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, I<f>κ</f>B kinase-#x03B5; and TANK-binding kinase-1, establishing a first canonical virus-induced IRF-3 activating pathway.
- Subjects
INTERFERONS; LYMPHOKINES; ANTINEOPLASTIC agents; GLYCOPROTEINS
- Publication
FEBS Letters, 2004, Vol 567, Issue 2/3, p230
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2004.04.069