Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase - PubMed (original) (raw)

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

Y L Yang et al. EMBO J. 1995.

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%). 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-gamma 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-kappa B 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.

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References

1. 1. J Biol Chem. 1991 Aug 25;266(24):16073-7 - PubMed
2. 1. J Biol Chem. 1992 Apr 15;267(11):7671-6 - PubMed
3. 1. Nature. 1992 Apr 16;356(6370):577-82 - PubMed
4. 1. EMBO J. 1992 Apr;11(4):1553-62 - PubMed
5. 1. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5447-51 - PubMed

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