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

EMBO J. 1995 Dec 15;14(24):6095-106. doi: 10.1002/j.1460-2075.1995.tb00300.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • DNA Primers / genetics
  • Encephalomyocarditis virus / pathogenicity
  • Gene Expression Regulation / drug effects
  • Interferon Type I / genetics
  • Interferons / pharmacology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Poly I-C / pharmacology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Signal Transduction
  • eIF-2 Kinase


  • DNA Primers
  • Interferon Type I
  • NF-kappa B
  • Interferons
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase
  • Poly I-C