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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7073
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pubmed:dateCreated |
2006-1-12
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pubmed:abstractText |
Toll-like receptors (TLRs) are activated by pathogen-associated molecular patterns to induce innate immune responses and production of pro-inflammatory cytokines, interferons and anti-inflammatory cytokines. TLRs activate downstream effectors through adaptors that contain Toll/interleukin-1 receptor (TIR) domains, but the mechanisms accounting for diversification of TLR effector functions are unclear. To dissect biochemically TLR signalling, we established a system for isolating signalling complexes assembled by dimerized adaptors. Using MyD88 as a prototypical adaptor, we identified TNF receptor-associated factor 3 (TRAF3) as a new component of TIR signalling complexes that is recruited along with TRAF6. Using myeloid cells from TRAF3- and TRAF6-deficient mice, we show that TRAF3 is essential for the induction of type I interferons (IFN) and the anti-inflammatory cytokine interleukin-10 (IL-10), but is dispensable for expression of pro-inflammatory cytokines. In fact, TRAF3-deficient cells overproduce pro-inflammatory cytokines owing to defective IL-10 production. Despite their structural similarity, the functions of TRAF3 and TRAF6 are largely distinct. TRAF3 is also recruited to the adaptor TRIF (Toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta) and is required for marshalling the protein kinase TBK1 (also called NAK) into TIR signalling complexes, thereby explaining its unique role in activation of the IFN response.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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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/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
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/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/TICAM-1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 3,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Tbk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:BlagoevBlagoyB,
pubmed-author:FiegE LEL,
pubmed-author:HäckerGeorgG,
pubmed-author:HäckerHansH,
pubmed-author:HsuLi-ChungLC,
pubmed-author:KampsMark PMP,
pubmed-author:KarinMichaelM,
pubmed-author:KratchmarovaIrinaI,
pubmed-author:MannMatthiasM,
pubmed-author:RedeckeVanessaV,
pubmed-author:WagnerHermannH,
pubmed-author:WangGang GGG
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pubmed:issnType |
Electronic
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pubmed:day |
12
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pubmed:volume |
439
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
204-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16306937-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16306937-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:16306937-Animals,
pubmed-meshheading:16306937-Antigens, Differentiation,
pubmed-meshheading:16306937-Cell Line,
pubmed-meshheading:16306937-Dimerization,
pubmed-meshheading:16306937-Gene Expression Regulation,
pubmed-meshheading:16306937-Immunity, Innate,
pubmed-meshheading:16306937-Interferons,
pubmed-meshheading:16306937-Interleukin-10,
pubmed-meshheading:16306937-Mice,
pubmed-meshheading:16306937-Myeloid Cells,
pubmed-meshheading:16306937-Myeloid Differentiation Factor 88,
pubmed-meshheading:16306937-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16306937-Receptors, Immunologic,
pubmed-meshheading:16306937-Signal Transduction,
pubmed-meshheading:16306937-Substrate Specificity,
pubmed-meshheading:16306937-TNF Receptor-Associated Factor 3,
pubmed-meshheading:16306937-TNF Receptor-Associated Factor 6,
pubmed-meshheading:16306937-Toll-Like Receptors
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pubmed:year |
2006
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pubmed:articleTitle |
Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6.
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pubmed:affiliation |
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. Hans.Haecker@stjude.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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