Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase

Yi Li Yang, Luiz F.L. Reis, Jovan Paylovic, Sano Aguzzi, Reinhold Schäfer, Aseem Kumar, Bryan R.G. Williams, Michel Aguet, Charles Weissmann

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Abstract

Double-stranded RNA-dependent protein kinase (PKR) has been implicated in interferon (IFN) induction, antiviral response and tumor suppression. We have generated mice devoid of functional PKR (Pkr(o/o)). Although the mice are physically normal and the induction of type I IFN genes by poly(I) poly(C) (pIC) and virus is unimpaired, the antiviral response induced by IFN-γ and pIC was diminished. However, in embryo fibroblasts from Pkr knockout mice, the induction of type I IFN as well as the activation of NF-κB by pIC, were strongly impaired but restored by priming with IFN. Thus, PKR is not directly essential for responses to pIC, and a pIC-responsive system independent of PKR is induced by IFN. No evidence of the tumor suppressor activity of PKR was demonstrated.

Original languageEnglish
Pages (from-to)6095-6106
Number of pages12
JournalThe EMBO Journal
Volume14
Issue number24
Publication statusPublished - 1 Dec 1995
Externally publishedYes

Keywords

  • Antiviral response
  • Double-stranded RNA-dependent protein kinase
  • Interferon induction
  • Tumor suppression

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