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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• 作者：Nora Taghavi ; Charles E. Samuel ; ^{samuel@lifesci.ucsb.edu}
• 关键词：PKR ; Protein kinase ; Interferon ; Innate immunity
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：5 June, 2012
• 卷：427
• 期：2
• 页码：208-216
• 文件大小：929 K

摘要

The protein kinase regulated by RNA (PKR) enhances both activation of mitogen-activated protein kinases and the induction of interferon beta (IFN-尾) 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-尾 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-尾 induction. Furthermore, inhibition of virus growth was observed with C^ko-infected PKR^kd cells complemented with PKR but not with PKZ.