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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
1999-5-3
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pubmed:abstractText |
Several mitogen-activated protein kinase kinase kinases play critical roles in nuclear factor-kappaB (NF-kappaB) activation. We recently reported that the overexpression of transforming growth factor-beta-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, together with its activator TAK1-binding protein 1 (TAB1) stimulates NF-kappaB activation. Here we investigated the molecular mechanism of TAK1-induced NF-kappaB activation. Dominant negative mutants of IkappaB kinase (IKK) alpha and IKKbeta inhibited TAK1-induced NF-kappaB activation. TAK1 activated IKKalpha and IKKbeta in the presence of TAB1. IKKalpha and IKKbeta were coimmunoprecipitated with TAK1 in the absence of TAB1. TAB1-induced TAK1 activation promoted the dissociation of active forms of IKKalpha and IKKbeta from active TAK1, whereas the IKK mutants remained to interact with active TAK1. Furthermore, tumor necrosis factor-alpha activated endogenous TAK1, and the kinase-negative TAK1 acted as a dominant negative inhibitor against tumor necrosis factor-alpha-induced NF-kappaB activation. These results demonstrated a novel signaling pathway to NF-kappaB activation through TAK1 in which TAK1 may act as a regulatory kinase of IKKs.
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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/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
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 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP kinase kinase kinase 7,
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/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/TAB1 protein, MAPKKK activator...,
http://linkedlifedata.com/resource/pubmed/chemical/TAB1 protein, human
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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 |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10641-8
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:10187861-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10187861-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10187861-Carrier Proteins,
pubmed-meshheading:10187861-Enzyme Activation,
pubmed-meshheading:10187861-HeLa Cells,
pubmed-meshheading:10187861-Humans,
pubmed-meshheading:10187861-I-kappa B Kinase,
pubmed-meshheading:10187861-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10187861-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:10187861-MAP Kinase Kinase Kinases,
pubmed-meshheading:10187861-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10187861-NF-kappa B,
pubmed-meshheading:10187861-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10187861-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:10187861-Serine
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pubmed:year |
1999
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pubmed:articleTitle |
Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation.
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pubmed:affiliation |
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 16-89 Kashima 3-chome, Yodogawa-ku, Osaka 532-8505, Japan.
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pubmed:publicationType |
Journal Article
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