Rac1 and PAK1 are upstream of IKK‐ε and TBK‐1 in the viral activation of interferon regulatory factor‐3
2004; Wiley; Volume: 567; Issue: 2-3 Linguagem: Inglês
10.1016/j.febslet.2004.04.069
ISSN1873-3468
AutoresChristina Ehrhardt, Christian Kardinal, Walter J. Wurzer, Thorsten Wolff, Christoph von Eichel‐Streiber, Stephan Pleschka, Oliver Planz, Stephan Ludwig,
Tópico(s)NF-κB Signaling Pathways
ResumoThe 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 κ B kinase‐ε and TANK‐binding kinase‐1, establishing a first canonical virus‐induced IRF‐3 activating pathway.
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