{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:06:19Z","timestamp":1791252379206,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"6980","license":[{"start":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T00:00:00Z","timestamp":1078099200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2004,3]]},"DOI":"10.1038\/nature02405","type":"journal-article","created":{"date-parts":[[2004,3,17]],"date-time":"2004-03-17T18:40:32Z","timestamp":1079548832000},"page":"341-345","source":"Crossref","is-referenced-by-count":299,"title":["The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4"],"prefix":"10.1038","volume":"428","author":[{"given":"Li-Chung","family":"Hsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Mo Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kezhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Li","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randal J.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald G.","family":"Guiney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"BFnature02405_CR1","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/35021228","volume":"406","author":"A Aderem","year":"2000","unstructured":"Aderem, A. & Ulevitch, R. J. Toll-like receptors in the induction of the innate immune response. Nature 406, 782\u2013787 (2000)","journal-title":"Nature"},{"key":"BFnature02405_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/35100529","volume":"1","author":"R Medzhitov","year":"2001","unstructured":"Medzhitov, R. Toll-like receptors and innate immunity. Nature Rev. Immunol. 1, 135\u2013145 (2001)","journal-title":"Nature Rev. Immunol."},{"key":"BFnature02405_CR3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1146\/annurev.micro.53.1.155","volume":"53","author":"Y Weinrauch","year":"1999","unstructured":"Weinrauch, Y. & Zychlinsky, A. The induction of apoptosis by bacterial pathogens. Annu. Rev. Microbiol. 53, 155\u2013187 (1999)","journal-title":"Annu. Rev. Microbiol."},{"key":"BFnature02405_CR4","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1126\/science.1073163","volume":"297","author":"JM Park","year":"2002","unstructured":"Park, J. M., Greten, F. R., Li, Z. W. & Karin, M. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297, 2048\u20132051 (2002)","journal-title":"Science"},{"key":"BFnature02405_CR5","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","volume":"282","author":"A Poltorak","year":"1998","unstructured":"Poltorak, A. et al. Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085\u20132088 (1998)","journal-title":"Science"},{"key":"BFnature02405_CR6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/41131","volume":"388","author":"R Medzhitov","year":"1997","unstructured":"Medzhitov, R., Preston-Hurlburt, P. & Janeway, C. A. Jr A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394\u2013397 (1997)","journal-title":"Nature"},{"key":"BFnature02405_CR7","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/nature01889","volume":"424","author":"K Hoebe","year":"2003","unstructured":"Hoebe, K. et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424, 743\u2013748 (2003)","journal-title":"Nature"},{"key":"BFnature02405_CR8","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1038\/ni986","volume":"4","author":"M Yamamoto","year":"2003","unstructured":"Yamamoto, M. et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nature Immunol. 4, 1144\u20131150 (2003)","journal-title":"Nature Immunol."},{"key":"BFnature02405_CR9","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S1074-7613(00)80086-2","volume":"11","author":"T Kawai","year":"1999","unstructured":"Kawai, T., Adachi, O., Ogawa, T., Takeda, K. & Akira, S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115\u2013122 (1999)","journal-title":"Immunity"},{"key":"BFnature02405_CR10","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1046\/j.1365-2443.1999.00265.x","volume":"4","author":"A Naito","year":"1999","unstructured":"Naito, A. et al. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 4, 353\u2013362 (1999)","journal-title":"Genes Cells"},{"key":"BFnature02405_CR11","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/ni0302-221","volume":"3","author":"M Karin","year":"2002","unstructured":"Karin, M. & Lin, A. NF-\u03baB at the crossroads of life and death. Nature Immunol. 3, 221\u2013227 (2002)","journal-title":"Nature Immunol."},{"key":"BFnature02405_CR12","doi-asserted-by":"publisher","first-page":"4630","DOI":"10.4049\/jimmunol.170.9.4630","volume":"170","author":"ZW Li","year":"2003","unstructured":"Li, Z. W., Omori, S. A., Labuda, T., Karin, M. & Rickert, R. C. Ikk\u03b2 is required for peripheral B cell survival and proliferation. J. Immunol. 170, 4630\u20134637 (2003)","journal-title":"J. Immunol."},{"key":"BFnature02405_CR13","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.7660125","volume":"269","author":"R Kuhn","year":"1995","unstructured":"Kuhn, R., Schwenk, F., Aguet, M. & Rajewsky, K. Inducible gene targeting in mice. Science 269, 1427\u20131429 (1995)","journal-title":"Science"},{"key":"BFnature02405_CR14","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/ni0901-835","volume":"2","author":"T Horng","year":"2001","unstructured":"Horng, T., Barton, G. M. & Medzhitov, R. TIRAP: an adapter molecule in the Toll signaling pathway. Nature Immunol. 2, 835\u2013841 (2001)","journal-title":"Nature Immunol."},{"key":"BFnature02405_CR15","first-page":"116935","volume":"96","author":"RJ Kaufman","year":"1999","unstructured":"Kaufman, R. J. Double-stranded RNA-activated protein kinase mediated virus-induced apoptosis: a new role for an old actor. Proc. Natl Acad. Sci. USA 96, 116935 (1999)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature02405_CR16","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/S1074-7613(00)80146-6","volume":"11","author":"WM Chu","year":"1999","unstructured":"Chu, W. M. et al. JNK2 and IKK\u03b2 are required for activating the innate response to viral infection. Immunity 11, 721\u2013731 (1999)","journal-title":"Immunity"},{"key":"BFnature02405_CR17","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1128\/CMR.14.4.778-809.2001","volume":"14","author":"CE Samuel","year":"2001","unstructured":"Samuel, C. E. Antiviral actions of interferons. Clin. Microbiol. Rev. 14, 778\u2013809 (2001)","journal-title":"Clin. Microbiol. Rev."},{"key":"BFnature02405_CR18","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1182\/blood.V98.3.736","volume":"98","author":"M Lehner","year":"2001","unstructured":"Lehner, M., Felzmann, T., Clodi, K. & Holter, W. Type I interferons in combination with bacterial stimuli induce apoptosis of monocyte-derived dendritic cells. Blood 98, 736\u2013742 (2001)","journal-title":"Blood"},{"key":"BFnature02405_CR19","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1126\/science.8009221","volume":"264","author":"U Muller","year":"1994","unstructured":"Muller, U. et al. Functional role of type I and type II interferons in antiviral defense. Science 264, 1918\u20131921 (1994)","journal-title":"Science"},{"key":"BFnature02405_CR20","doi-asserted-by":"publisher","first-page":"41620","DOI":"10.1074\/jbc.M103674200","volume":"276","author":"X Saelens","year":"2001","unstructured":"Saelens, X., Kalai, M. & Vandenabeele, P. Translation inhibition in apoptosis: caspase-dependent PKR activation and eIF2-alpha phosphorylation. J. Biol. Chem. 276, 41620\u201341628 (2001)","journal-title":"J. Biol. Chem."},{"key":"BFnature02405_CR21","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature01783","volume":"424","author":"SS Diebold","year":"2003","unstructured":"Diebold, S. S. et al. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424, 324\u2013328 (2003)","journal-title":"Nature"},{"key":"BFnature02405_CR22","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1016\/S1097-2765(01)00265-9","volume":"7","author":"D Scheuner","year":"2001","unstructured":"Scheuner, D. et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7, 1165\u20131176 (2001)","journal-title":"Mol. Cell"},{"key":"BFnature02405_CR23","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.1128\/JVI.74.8.3781-3792.2000","volume":"74","author":"C Heylbroeck","year":"2000","unstructured":"Heylbroeck, C. et al. The IRF-3 transcription factor mediates Sendai virus-induced apoptosis. J. Virol. 74, 3781\u20133792 (2000)","journal-title":"J. Virol."},{"key":"BFnature02405_CR24","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/S1074-7613(00)00053-4","volume":"13","author":"M Sato","year":"2000","unstructured":"Sato, M. et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-\u03b1\/\u03b2 gene induction. Immunity 13, 539\u2013548 (2000)","journal-title":"Immunity"},{"key":"BFnature02405_CR25","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1126\/science.290.5496.1594","volume":"290","author":"K Orth","year":"2000","unstructured":"Orth, K. et al. Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like protein protease. Science 290, 1594\u20131597 (2000)","journal-title":"Science"},{"key":"BFnature02405_CR26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrm1104","volume":"4","author":"CM Rosenberger","year":"2003","unstructured":"Rosenberger, C. M. & Finlay, B. B. Phagocyte sabotage: disruption of macrophage signalling by bacterial pathogens. Nature Rev. Mol. Cell Biol. 4, 385\u2013396 (2003)","journal-title":"Nature Rev. Mol. Cell Biol."},{"key":"BFnature02405_CR27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1089\/088282402317340224","volume":"15","author":"RK Durbin","year":"2002","unstructured":"Durbin, R. K., Mertz, S. E., Koromilas, A. E. & Durbin, J. E. PKR protection against intranasal vesicular stomatitis virus infection is mouse strain dependent. Viral Immunol. 15, 41\u201351 (2002)","journal-title":"Viral Immunol."},{"key":"BFnature02405_CR28","doi-asserted-by":"publisher","first-page":"6095","DOI":"10.1002\/j.1460-2075.1995.tb00300.x","volume":"14","author":"YL Yang","year":"1995","unstructured":"Yang, Y. L. et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 14, 6095\u20136106 (1995)","journal-title":"EMBO J."},{"key":"BFnature02405_CR29","doi-asserted-by":"publisher","first-page":"7126","DOI":"10.1128\/IAI.70.12.7126-7135.2002","volume":"70","author":"SH Browne","year":"2002","unstructured":"Browne, S. H., Lesnick, M. L. & Guiney, D. G. Genetic requirements for salmonella-induced cytopathology in human monocyte-derived macrophages. Infect. Immun. 70, 7126\u20137135 (2002)","journal-title":"Infect. Immun."},{"key":"BFnature02405_CR30","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1128\/IAI.71.3.1513-1519.2003","volume":"71","author":"Y Zhang","year":"2003","unstructured":"Zhang, Y. & Bliska, J. B. Role of Toll-like receptor signaling in the apoptotic response of macrophages to Yersinia infection. Infect. Immun. 71, 1513\u20131519 (2003)","journal-title":"Infect. Immun."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature02405.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature02405","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature02405.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T18:21:55Z","timestamp":1684434115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature02405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3]]},"references-count":30,"journal-issue":{"issue":"6980","published-print":{"date-parts":[[2004,3]]}},"alternative-id":["BFnature02405"],"URL":"https:\/\/doi.org\/10.1038\/nature02405","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,3]]}}}