JNK2 and IKKβ are required for activating the innate response to viral infection

Wen Ming Chu, Derek Ostertag, Zhi Wei Li, Lufen Chang, Yi Chen, Yinling Hu, Bryan Williams, Jacques Perrault, Michael Karin

Research output: Contribution to journalArticleResearchpeer-review

330 Citations (Scopus)

Abstract

Viral infection or double-stranded (ds) RNA induce interferons (IFN) and other cytokines. Transcription factors mediating IFN induction are known, but the signaling pathways that regulate them are less clear. We now describe two such pathways. The first pathway leading to NF-κB depends on the dsRNA- responsive protein kinase (PKR), which in turn activates IκB kinase (IKK) through the IKKβ subunit. The second viral- and dsRNA-responsive pathway is PKR independent and involves Jun kinase (JNK) activation leading to stimulation of AP-1. Both IKKβ and JNK2 are essential for efficient induction of type I IFN and other cytokines in response to viral infection or dsRNA. This study establishes a general role for these kinases in activation of innate immune responses.

Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalImmunity
Volume11
Issue number6
DOIs
Publication statusPublished - Dec 1999
Externally publishedYes

Cite this