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Deficient Signaling in Mice Devoid of Double-stranded RNA-dependent Protein Kinase

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Journal EMBO J
Date 1995 Dec 15
PMID 8557029
Citations 277
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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%). 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.
Icely P, Gros P, Bergeron J, DeVault A, Afar D, Bell J . TIK, a novel serine/threonine kinase, is recognized by antibodies directed against phosphotyrosine. J Biol Chem. 1991; 266(24):16073-7. View

2.
Patel R, Sen G . Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. J Biol Chem. 1992; 267(11):7671-6. View

3.
Bueler H, Fischer M, Lang Y, Bluethmann H, Lipp H, DeArmond S . Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature. 1992; 356(6370):577-82. DOI: 10.1038/356577a0. View

4.
Chong K, Feng L, Schappert K, Meurs E, Donahue T, Friesen J . Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO J. 1992; 11(4):1553-62. PMC: 556604. DOI: 10.1002/j.1460-2075.1992.tb05200.x. View

5.
Feng G, Chong K, Kumar A, Williams B . Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase. Proc Natl Acad Sci U S A. 1992; 89(12):5447-51. PMC: 49309. DOI: 10.1073/pnas.89.12.5447. View