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Protein kinase PKR catalytic activity is required for the PKR-dependent activation of mitogen-activated protein kinases and amplification of interferon beta induction following virus infection.

Taghavi N., Samuel C.E.

The protein kinase regulated by RNA (PKR) enhances both activation of mitogen-activated protein kinases and the induction of interferon beta (IFN-β) by measles virus defective in C-protein expression (C(ko)). Here we used complementation of human cell lines stably deficient in PKR (PKR(kd)) to probe the basis of these PKR-mediated responses. We found that PKR(kd) HeLa and amnion U cell lines were defective for virus-mediated activation of IFN induction signaling components compared to PKR-sufficient control cells. Complementation of PKR(kd) cells with wildtype PKR, but not with PKR mutants defective in either catalytic activity or dsRNA-binding activity, restored JNK, p38 and ATF-2 phosphorylation and enhanced IFN-β induction following infection. By contrast to mammalian PKR, the Z-DNA binding domain-containing fish homologue of PKR, PKZ, lacked the capacity to enhance C(ko) virus-mediated IFN-β induction. Furthermore, inhibition of virus growth was observed with C(ko)-infected PKR(kd) cells complemented with PKR but not with PKZ.

Virology 427:208-216(2012) [PubMed] [Europe PMC]

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