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.
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Taghavi N, Samuel CE
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.
Virology. 2012 Jun 5;427(2):208-16. doi: 10.1016/j.virol.2012.01.029. Epub 2012 Mar 3.
- PubMed ID
- 22381929 [ View in PubMed]
- Abstract
The protein kinase regulated by RNA (PKR) enhances both activation of mitogen-activated protein kinases and the induction of interferon beta (IFN-beta) 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-beta 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-beta induction. Furthermore, inhibition of virus growth was observed with C(ko)-infected PKR(kd) cells complemented with PKR but not with PKZ.