Abstract
The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. Here we report the identification of TAB2, a novel intermediate in the IL-1 pathway that functionally links TAK1 to TRAF6. Expression of TAB2 induces JNK and NF-kappaB activation, whereas a dominant-negative mutant TAB2 impairs their activation by IL-1. IL-1 stimulates translocation of TAB2 from the membrane to the cytosol where it mediates the IL-1-dependent association of TAK1 with TRAF6. These results define TAB2 as an adaptor linking TAK1 and TRAF6 and as a mediator of TAK1 activation in the IL-1 signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Biological Transport
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Membrane / metabolism
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Cloning, Molecular
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Cytosol / metabolism
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Enzyme Activation
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Gene Library
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Humans
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Interleukin-1 / pharmacology*
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinases / metabolism*
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Mitogen-Activated Protein Kinases / metabolism
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Models, Biological
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Molecular Sequence Data
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NF-kappa B / metabolism
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Protein Binding
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Proteins / metabolism*
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Signal Transduction
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TNF Receptor-Associated Factor 6
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Two-Hybrid System Techniques
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Interleukin-1
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NF-kappa B
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Proteins
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TAB2 protein, human
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TNF Receptor-Associated Factor 6
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinases
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MAP kinase kinase kinase 7