{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:14:55Z","timestamp":1791321295523,"version":"4.3.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) play important roles in the host innate immune response. The protein kinase regulated by RNA (PKR) is implicated in p38 MAPK activation in response to proinflammatory signals in mouse embryonic fibroblasts. To test the role of PKR in the activation of p38 and JNK MAPKs in human cells following viral infection, HeLa cells made stably deficient in PKR by using an RNA interference strategy were compared to cells with sufficient PKR. The phosphorylation of both p38 and JNK in cells with sufficient PKR was activated following either infection with an E3L deletion (\u0394E3L) mutant of vaccinia virus or transfection with double-stranded RNA (dsRNA) in the absence of infection with wild-type vaccinia virus. The depletion of PKR by stable knockdown impaired the phosphorylation of both p38 and JNK induced by either the \u0394E3L mutant virus or dsRNA but not that induced by tumor necrosis factor alpha. The PKR-dependent activation of MAPKs in \u0394E3L mutant-infected cells was abolished by treatment with cytosine \u03b2-\n            <jats:sc>d<\/jats:sc>\n            -arabinoside. The complementation of PKR-deficient cells with the human PKR wild-type protein, but not with the PKR catalytic mutant (K296R) protein, restored p38 and JNK phosphorylation following \u0394E3L mutant virus infection. Transient small interfering RNA knockdown established that the p38 and JNK kinase activation following \u0394E3L infection was dependent upon RIG-I-like receptor signal transduction pathway components, including the mitochondrial adapter IPS-1 protein.\n          <\/jats:p>","DOI":"10.1128\/jvi.00224-09","type":"journal-article","created":{"date-parts":[[2009,3,26]],"date-time":"2009-03-26T01:09:42Z","timestamp":1238029782000},"page":"5718-5725","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Protein Kinase PKR-Dependent Activation of Mitogen-Activated Protein Kinases Occurs through Mitochondrial Adapter IPS-1 and Is Antagonized by Vaccinia Virus E3L"],"prefix":"10.1128","volume":"83","author":[{"given":"Ping","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey O.","family":"Langland","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram L.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, and School of Life Sciences, Arizona State University, Tempe, Arizona 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106"},{"name":"Biomolecular Sciences and Engineering Program, University of California, Santa Barbara, California 93106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35099560"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2007.11.006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1865"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1256"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1292"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.10.6605-6608.1995"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.7.1.71-76.1971"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109910200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01305-08"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.10.4502-4512.2004"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.16.4292"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.09.024"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.2.617-627.2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2005.25.749"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1243"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.2.406"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1479"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.03.012"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00607-06"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305893200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2035"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.4.2584-2596.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807888200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90733-6"},{"key":"e_1_3_2_26_2","first-page":"2849","volume":"2","year":"2001","unstructured":"Moss, B. 2001. 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