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PMID: 8557029 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 14 ·No. 24 ·1995-12-15 ·Pages 6095-106

Yang YL, Reis LF, Pavlovic J, Aguzzi A, Schäfer R, Kumar A, Williams BR, Aguet M, Weissmann C

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.

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,physiology Signal Transduction eIF-2 Kinase
Chemicals
DNA Primers Interferon Type I NF-kappa B Interferons Protein Serine-Threonine Kinases eIF-2 Kinase Poly I-C
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yang Y L
Institut für Molekularbiologie I, Universität Zürich, Switzerland.
Reis L F
Pavlovic J
Aguzzi A
Schäfer R
Kumar A
Williams B R
Aguet M
Weissmann C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-12-15
Pages
6095-106
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394734
Subset
IM
Grants
NIAID NIH HHS · AI 34039-02 · United States
External Links
PubMed source PMC Full Text View journal details
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