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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2004-3-8
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pubmed:abstractText |
Interferon regulatory factor (IRF)-3 is a critical transcription factor regulating innate immune responses against viral and bacterial infections. Signals activated by various pathogens are integrated by IRF-3 kinase, resulting in the specific phosphorylation of IRF-3 in the cytoplasm. This phosphorylation induces dimerization and association with the coactivators CREB-binding protein/p300, and the resultant complex activates the target genes in the nucleus. However, the phosphorylation sites that determine the active/inactive status of IRF-3 have been a source of controversy. In this study, we generated an antibody that specifically detects the phosphorylation of Ser-386 and used it as a probe. We found: 1) viral infection specifically induces phosphorylation of the Ser-386; 2) recently identified IRF-3 kinases (IKK-i/epsilon and TBK-1) phosphorylate Ser-386 and induce its dimerization; 3) phosphorylation of Ser-386 is exclusively observed with the dimer; 4) mutation at Ser-386 abolishes the dimerization potential; 5) a constitutively active 5D mutant designed to mimic phosphorylation of Ser/Thr residues other than Ser-385 and -386 is secondarily phosphorylated at Ser-386, presumably by an irrelevant kinase. These results strongly suggest that Ser-386 is the target of the IRF-3 kinase and critical determinant for the activation of IRF-3.
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IRF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Irf3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/TBK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tbk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/citrate-binding transport protein
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9698-702
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14703513-Amino Acid Sequence,
pubmed-meshheading:14703513-Animals,
pubmed-meshheading:14703513-Carrier Proteins,
pubmed-meshheading:14703513-Cell Line,
pubmed-meshheading:14703513-Crystallography, X-Ray,
pubmed-meshheading:14703513-Cytoplasm,
pubmed-meshheading:14703513-DNA-Binding Proteins,
pubmed-meshheading:14703513-Dimerization,
pubmed-meshheading:14703513-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:14703513-Genetic Vectors,
pubmed-meshheading:14703513-Humans,
pubmed-meshheading:14703513-I-kappa B Kinase,
pubmed-meshheading:14703513-Immunoblotting,
pubmed-meshheading:14703513-Interferon Regulatory Factor-3,
pubmed-meshheading:14703513-Mice,
pubmed-meshheading:14703513-Molecular Sequence Data,
pubmed-meshheading:14703513-Mutagenesis,
pubmed-meshheading:14703513-Mutation,
pubmed-meshheading:14703513-Phosphorylation,
pubmed-meshheading:14703513-Plasmids,
pubmed-meshheading:14703513-Protein Binding,
pubmed-meshheading:14703513-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14703513-Sequence Homology, Amino Acid,
pubmed-meshheading:14703513-Serine,
pubmed-meshheading:14703513-Transcription Factors,
pubmed-meshheading:14703513-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation.
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pubmed:affiliation |
Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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