Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase
Yang, Y.L.; Reis, L.F.; Pavlovic, J.; Aguzzi, A.; Schäfer, R.; Kumar, A.; Williams, B.R.; Aguet, M.; Weissmann, C.
EMBO Journal 14(24): 6095-6106
1995
ISSN/ISBN: 0261-4189 PMID: 8557029 Document Number: 447487
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) cntdot 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.