Abstract
The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase. Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) are both involved in subsequent steps of NF-kappaB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.
Publication types
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Comparative Study
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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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Antigens, Differentiation*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Humans
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JNK Mitogen-Activated Protein Kinases
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Membrane Glycoproteins*
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Membrane Proteins / metabolism*
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Mitogen-Activated Protein Kinases*
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Models, Immunological
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Molecular Sequence Data
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Monocytes / immunology
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Myeloid Differentiation Factor 88
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NF-kappa B / metabolism*
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Proteins / metabolism*
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Receptors, Cell Surface*
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Receptors, Immunologic / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction
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TNF Receptor-Associated Factor 6
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Toll-Like Receptors
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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MYD88 protein, human
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Membrane Glycoproteins
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Membrane Proteins
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Myeloid Differentiation Factor 88
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NF-kappa B
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Proteins
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Tumor Necrosis Factor
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TNF Receptor-Associated Factor 6
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Toll-Like Receptors
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases