Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase.
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.
Yang
Y L
YL
Institut für Molekularbiologie I, Universität Zürich, Switzerland.
Reis
L F
LF
Pavlovic
J
J
Aguzzi
A
A
Schäfer
R
R
Kumar
A
A
Williams
B R
BR
Aguet
M
M
Weissmann
C
C
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004686:Encephalomyocarditis virus / Q000472:pathogenicity; D005786:Gene Expression Regulation / Q000187:drug effects; D007370:Interferon Type I / Q000235:genetics; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D019892:eIF-2 Kinase
D017931:DNA Primers; D007370:Interferon Type I; D016328:NF-kappa B; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D011070:Poly I-C