The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4
dc.contributor.author | Hsu, L. C. | en_US |
dc.contributor.author | Park, Jin Mo | en_US |
dc.contributor.author | Zhang, K. Z. | en_US |
dc.contributor.author | Luo, Jun-Li | en_US |
dc.contributor.author | Maeda, S. | en_US |
dc.contributor.author | Kaufman, R. J. | en_US |
dc.contributor.author | Eckmann, L. | en_US |
dc.contributor.author | Guiney, D. G. | en_US |
dc.contributor.author | Karin, M. | en_US |
dc.date.accessioned | 2009-06-01T17:30:15Z | |
dc.date.available | 2009-06-01T17:30:15Z | |
dc.date.issued | 2004-03-18 | en_US |
dc.identifier.citation | Hsu, LC; Park, JM; Zhang, KZ; Luo, JL; Maeda, S; Kaufman, RJ; Eckmann, L; Guiney, DG; Karin, M. (2004) "The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4." Nature 428(6980): 341-345. <http://hdl.handle.net/2027.42/62666> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62666 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15029200&dopt=citation | en_US |
dc.description.abstract | Macrophages are pivotal constituents of the innate immune system, vital for recognition and elimination of microbial pathogens(1). Macrophages use Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns - including bacterial cell wall components, such as lipopolysaccharide or lipoteichoic acid, and viral nucleic acids, such as double-stranded (ds) RNA and in turn activate effector functions, including anti-apoptotic signalling pathways(2). Certain pathogens, however, such as Salmonella spp., Shigellae spp. and Yersiniae spp., use specialized virulence factors to overcome these protective responses and induce macrophage apoptosis(3). We found that the anthrax bacterium, Bacillus anthracis, selectively induces apoptosis of activated macrophages(4) through its lethal toxin, which prevents activation of the anti-apoptotic p38 mitogen-activated protein kinase(4). We now demonstrate that macrophage apoptosis by three different bacterial pathogens depends on activation of TLR4. Dissection of anti- and pro-apoptotic signalling events triggered by TLR4 identified the dsRNA responsive protein kinase PKR as a critical mediator of pathogen-induced macrophage apoptosis. The pro-apoptotic actions of PKR are mediated both through inhibition of protein synthesis and activation of interferon response factor 3. | en_US |
dc.format.extent | 493033 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/octet-stream | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4 | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Howard Hughes Med Inst, Dept Biol Chem, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA | en_US |
dc.contributor.affiliationother | Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA | en_US |
dc.identifier.pmid | 15029200 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62666/1/nature02405.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature02405 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | karinoffice@ucsd.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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