RNA-dependent protein kinase PKR is required for activation of NF-κB by INF-γ in a STAT1-independent pathway

Amitabha Deb, S. Jaharul Haque, Trine Mogensen, Robert H. Silverman, Bryan R.G. Williams

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101 Citations (Scopus)

Abstract

The IFN-inducible dsRNA-activated protein kinase PKR regulates protein synthesis through phosphorylation of eukaryotic initiation factor-2α. It also acts as a signal transducer for transcription factors NF-κB, IFN regulatory factor-1, and activating transcription factor-2. IFN-γ, a pleiotropic cytokine, elicits gene expression by activating the Janus kinase-STAT signaling pathway. IFN-γ can synergize with TNF-α to activate NF-κB in a number of cell lines. Here we show that IFN-γ alone can activate NF-κB, by a Janus kinase-1-mediated, but Stat1-independent, mechanism. NF-κB activation by IFN-γ is associated with degradation of IκB β. The IFN-γ response can be blocked by 2′,5′-oligoadenylate-linked antisense chimeras against PKR mRNA. There was no activation of NF-κB by IFN in PKR-null cells, indicating that PKR is required for IFN-γ signaling to NF-κB.

Original languageEnglish
Pages (from-to)6170-6180
Number of pages11
JournalJournal of Immunology
Volume166
Issue number10
Publication statusPublished - 15 May 2001
Externally publishedYes

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