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

Yi Li Yang; Luiz F.L. Reis; Jovan Paylovic; Sano Aguzzi; Reinhold Schäfer; Aseem Kumar; Bryan R.G. Williams; Michel Aguet; Charles Weissmann

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

Yi Li Yang, Luiz F.L. Reis, Jovan Paylovic, Sano Aguzzi, Reinhold Schäfer, Aseem Kumar, Bryan R.G. Williams, Michel Aguet, Charles Weissmann

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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(o/o)). 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-γ 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-κB 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.

Original language	English
Pages (from-to)	6095-6106
Number of pages	12
Journal	The EMBO Journal
Volume	14
Issue number	24
Publication status	Published - 1 Dec 1995
Externally published	Yes

Keywords

Antiviral response
Double-stranded RNA-dependent protein kinase
Interferon induction
Tumor suppression

Cite this

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title = "Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase",

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(o/o)). 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-γ 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-κB 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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author = "Yang, {Yi Li} and Reis, {Luiz F.L.} and Jovan Paylovic and Sano Aguzzi and Reinhold Sch{\"a}fer and Aseem Kumar and Williams, {Bryan R.G.} and Michel Aguet and Charles Weissmann",

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AU - Yang, Yi Li

AU - Reis, Luiz F.L.

AU - Paylovic, Jovan

AU - Aguzzi, Sano

AU - Schäfer, Reinhold

AU - Kumar, Aseem

AU - Williams, Bryan R.G.

AU - Aguet, Michel

AU - Weissmann, Charles

PY - 1995/12/1

Y1 - 1995/12/1

N2 - 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) poly(C) (pIC) and virus is unimpaired, the antiviral response induced by IFN-γ 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-κB 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.

AB - 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) poly(C) (pIC) and virus is unimpaired, the antiviral response induced by IFN-γ 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-κB 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.

KW - Antiviral response

KW - Double-stranded RNA-dependent protein kinase

KW - Interferon induction

KW - Tumor suppression

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JF - The EMBO Journal

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

Abstract

Keywords

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