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rdf:type |
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lifeskim:mentions |
umls-concept:C0017263,
umls-concept:C0031727,
umls-concept:C0032214,
umls-concept:C0035820,
umls-concept:C0040649,
umls-concept:C0063710,
umls-concept:C0169101,
umls-concept:C0205099,
umls-concept:C0441712,
umls-concept:C0600138,
umls-concept:C1417830,
umls-concept:C1948027
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pubmed:issue |
5
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pubmed:dateCreated |
2001-5-23
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pubmed:abstractText |
Mechanisms of fulminant gene induction during an inflammatory response were investigated using expression of the chemoattractant cytokine interleukin-8 (IL-8) as a model. Recently we found that coordinate activation of NF-kappaB and c-Jun N-terminal protein kinase (JNK) is required for strong IL-8 transcription, whereas the p38 MAP kinase (MAPK) pathway stabilizes the IL-8 mRNA. It is unclear how these pathways are coupled to the receptor for IL-1, an important physiological inducer of IL-8. Expression of the MAP kinase kinase kinase (MAPKKK) TAK1 together with its coactivator TAB1 in HeLa cells activated all three pathways and was sufficient to induce IL-8 formation, NF-kappaB + JNK2-mediated transcription from a minimal IL-8 promoter, and p38 MAPK-mediated stabilization of a reporter mRNA containing IL-8-derived regulatory mRNA sequences. Expression of a kinase-inactive mutant of TAK1 largely blocked IL-1-induced transcription and mRNA stabilization, as well as formation of endogenous IL-8. Truncated TAB1, lacking the TAK1 binding domain, or a TAK1-derived peptide containing a TAK1 autoinhibitory domain were also efficient in inhibition. These data indicate that the previously described three-pathway model of IL-8 induction is operative in response to a physiological stimulus, IL-1, and that the MAPKKK TAK1 couples the IL-1 receptor to both transcriptional and RNA-targeted mechanisms mediated by the three pathways.
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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/Globins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP kinase kinase kinase 7,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-8A,
http://linkedlifedata.com/resource/pubmed/chemical/TAB1 protein, MAPKKK activator...,
http://linkedlifedata.com/resource/pubmed/chemical/TAB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BroemerMM,
pubmed-author:DorrieAA,
pubmed-author:EnningaJJ,
pubmed-author:HoltmannHH,
pubmed-author:KalbleSS,
pubmed-author:KrachtMM,
pubmed-author:MatsumotoKK,
pubmed-author:Ninomiya-TsujiJJ,
pubmed-author:ReschKK,
pubmed-author:ThiefesAA,
pubmed-author:WilhelmAA,
pubmed-author:WilsonG FGF
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pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3508-16
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:11050078-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:11050078-Carrier Proteins,
pubmed-meshheading:11050078-Enzyme Activation,
pubmed-meshheading:11050078-Gene Expression Regulation,
pubmed-meshheading:11050078-Globins,
pubmed-meshheading:11050078-HeLa Cells,
pubmed-meshheading:11050078-Humans,
pubmed-meshheading:11050078-Interleukin-8,
pubmed-meshheading:11050078-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11050078-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:11050078-MAP Kinase Kinase 4,
pubmed-meshheading:11050078-MAP Kinase Kinase Kinases,
pubmed-meshheading:11050078-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:11050078-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11050078-Mutation,
pubmed-meshheading:11050078-NF-kappa B,
pubmed-meshheading:11050078-Promoter Regions, Genetic,
pubmed-meshheading:11050078-RNA, Messenger,
pubmed-meshheading:11050078-RNA Stability,
pubmed-meshheading:11050078-Receptors, Interleukin-1,
pubmed-meshheading:11050078-Receptors, Interleukin-8A,
pubmed-meshheading:11050078-Transcription, Genetic,
pubmed-meshheading:11050078-Transcriptional Activation,
pubmed-meshheading:11050078-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2001
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pubmed:articleTitle |
The MAPK kinase kinase TAK1 plays a central role in coupling the interleukin-1 receptor to both transcriptional and RNA-targeted mechanisms of gene regulation.
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pubmed:affiliation |
Institute of Pharmacology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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