Abstract
The interleukin-1 receptor (IL-1R) signaling pathway leads to nuclear factor kappa B (NF-kappaB) activation in mammals and is similar to the Toll pathway in Drosophila: the IL-1R-associated kinase (IRAK) is homologous to Pelle. Two additional proximal mediators were identified that are required for IL-1R-induced NF-kappaB activation: IRAK-2, a Pelle family member, and MyD88, a death domain-containing adapter molecule. Both associate with the IL-1R signaling complex. Dominant negative forms of either attenuate IL-1R-mediated NF-kappaB activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation.
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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Carrier Proteins / metabolism
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Cell Line
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Drosophila Proteins*
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Humans
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Interleukin-1 / metabolism*
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Interleukin-1 Receptor-Associated Kinases
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Molecular Sequence Data
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Myeloid Differentiation Factor 88
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NF-kappa B / metabolism
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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Receptors, Immunologic*
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Receptors, Interleukin-1 / metabolism*
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Sequence Alignment
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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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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Carrier Proteins
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Drosophila Proteins
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Interleukin-1
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MYD88 protein, human
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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, Immunologic
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Receptors, Interleukin-1
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TNF Receptor-Associated Factor 6
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Protein Kinases
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pll protein, Drosophila
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Interleukin-1 Receptor-Associated Kinases
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Protein Serine-Threonine Kinases