title: 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.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Taghavi
authors.forename: Charles E
authors.initials: CE
authors.lastname: Samuel
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D015398:Signal Transduction; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D016899:Interferon-beta; D019892:eIF-2 Kinase; D020929:Mitogen-Activated Protein Kinase Kinases