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rdf:type |
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lifeskim:mentions |
umls-concept:C0037083,
umls-concept:C0063710,
umls-concept:C0152060,
umls-concept:C0205154,
umls-concept:C0205224,
umls-concept:C0851827,
umls-concept:C1306235,
umls-concept:C1521761,
umls-concept:C1701901,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1710082,
umls-concept:C1823491,
umls-concept:C1843476
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pubmed:issue |
5
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pubmed:dateCreated |
2004-8-23
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pubmed:abstractText |
Signaling pathways from TLRs are mediated by the Toll/IL-1R (TIR) domain-containing adaptor molecules. TNF receptor-associated factor (TRAF) 6 is thought to activate NF-kappaB and MAPKs downstream of these TIR domain-containing proteins to induce production of inflammatory cytokines. However, the precise role of TRAF6 in signaling from individual TLRs has not been appropriately addressed. We analyzed macrophages from TRAF6-deficient mice and made the following observations. In the absence of TRAF6, 1) ligands for TLR2, TLR5, TLR7, and TLR9 failed to induce activation of NF-kappaB and MAPKs or production of inflammatory cytokines; 2) TLR4 ligand-induced cytokine production was remarkably reduced and activation of NF-kappaB and MAPKs was observed, albeit with delayed kinetics; and 3) in contrast with previously reported findings, TLR3 signaling was not affected. These results indicate that TRAF6 is essential for MyD88-dependent signaling but is not required for TIR domain-containing adaptor-inducing IFN-beta (TRIF)-dependent signaling.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myd88 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/TICAM-1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TIRAP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TIRAP protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 3,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 5,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 7,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 9,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2913-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15322147-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:15322147-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:15322147-Animals,
pubmed-meshheading:15322147-Antigens, Differentiation,
pubmed-meshheading:15322147-Humans,
pubmed-meshheading:15322147-Macrophages,
pubmed-meshheading:15322147-Membrane Glycoproteins,
pubmed-meshheading:15322147-Mice,
pubmed-meshheading:15322147-Myeloid Differentiation Factor 88,
pubmed-meshheading:15322147-Proteins,
pubmed-meshheading:15322147-Receptors, Cell Surface,
pubmed-meshheading:15322147-Receptors, Immunologic,
pubmed-meshheading:15322147-Receptors, Interleukin-1,
pubmed-meshheading:15322147-Signal Transduction,
pubmed-meshheading:15322147-TNF Receptor-Associated Factor 6,
pubmed-meshheading:15322147-Toll-Like Receptor 2,
pubmed-meshheading:15322147-Toll-Like Receptor 3,
pubmed-meshheading:15322147-Toll-Like Receptor 4,
pubmed-meshheading:15322147-Toll-Like Receptor 5,
pubmed-meshheading:15322147-Toll-Like Receptor 7,
pubmed-meshheading:15322147-Toll-Like Receptor 9,
pubmed-meshheading:15322147-Toll-Like Receptors
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pubmed:year |
2004
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pubmed:articleTitle |
Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling.
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pubmed:affiliation |
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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