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rdf:type |
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lifeskim:mentions |
umls-concept:C0020792,
umls-concept:C0021755,
umls-concept:C0063710,
umls-concept:C0208973,
umls-concept:C0530129,
umls-concept:C0599697,
umls-concept:C1334201,
umls-concept:C1336666,
umls-concept:C1449799,
umls-concept:C1514762,
umls-concept:C1517892,
umls-concept:C1704666,
umls-concept:C1836941
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pubmed:issue |
14
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pubmed:dateCreated |
2003-3-31
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pubmed:databankReference |
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pubmed:abstractText |
Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the Toll/interleukin-1 (IL-1) receptor family by interacting with IL-1 receptor-associated kinase-1 (IRAK-1) after IRAK-1 is released from the receptor-MyD88 complex upon IL-1 stimulation. However, the molecular mechanisms underlying regulation of the IRAK-1/TRAF6 interaction are largely unknown. We have identified TIFA, a TRAF-interacting protein with a forkhead-associated (FHA) domain. The FHA domain is a motif known to bind directly to phosphothreonine and phosphoserine. In transient transfection assays, TIFA activates NFkappaBeta and c-Jun amino-terminal kinase. However, TIFA carrying a mutation that abolishes TRAF6 binding or mutations in the FHA domain that are known to abolish FHA domain binding to phosphopeptide fails to activate NFkappaBeta and c-Jun amino-terminal kinase. TIFA, when overexpressed, binds both TRAF6 and IRAK-1 and significantly enhances the IRAK-1/TRAF6 interaction. Furthermore, analysis of endogenous proteins indicates that TIFA associates with TRAF6 constitutively, whereas it associates with IRAK-1 in an IL-1 stimulation-dependent manner in vivo. Thus, TIFA is likely to mediate IRAK-1/TRAF6 interaction upon IL-1 stimulation.
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1 Receptor-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/T2bp protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AkiyamaTaishinT,
pubmed-author:GohdaJinJ,
pubmed-author:InoueJun-IchiroJ,
pubmed-author:KatoHirokiH,
pubmed-author:MoriyaAyakaA,
pubmed-author:OkamotoYoshinariY,
pubmed-author:OtsukaMasamiM,
pubmed-author:SembaKentaroK,
pubmed-author:TakatsunaHiroshiH,
pubmed-author:UmezawaKazuoK,
pubmed-author:YamagataYurikoY
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12144-50
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12566447-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12566447-Animals,
pubmed-meshheading:12566447-Carrier Proteins,
pubmed-meshheading:12566447-Female,
pubmed-meshheading:12566447-Interleukin-1,
pubmed-meshheading:12566447-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:12566447-Mice,
pubmed-meshheading:12566447-Mice, Inbred ICR,
pubmed-meshheading:12566447-Molecular Sequence Data,
pubmed-meshheading:12566447-NF-kappa B,
pubmed-meshheading:12566447-Protein Kinases,
pubmed-meshheading:12566447-Proteins,
pubmed-meshheading:12566447-Receptors, Interleukin-1,
pubmed-meshheading:12566447-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:12566447-Sequence Homology, Amino Acid,
pubmed-meshheading:12566447-Signal Transduction,
pubmed-meshheading:12566447-TNF Receptor-Associated Factor 6
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pubmed:year |
2003
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pubmed:articleTitle |
Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling.
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pubmed:affiliation |
Division of Cellular and Molecular Biology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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