Abstract
The interleukin-1 receptor-associated kinase (IRAK) was first described as a signal transducer for interleukin-1 (IL-1) and has later been implicated in signal transduction of other members of the Toll/IL-1 receptor family. We now report the identification and characterization of a novel IRAK-like molecule. In contrast to the ubiquitously expressed IRAK and IRAK-2, this new IRAK-like molecule is found mainly in cells of monomyeloic origin and is, therefore, designated IRAK-M. Although IRAK-M and IRAK-2 exhibit only a negligible autophosphorylation activity, they can reconstitute the IL-1 response in a 293 mutant cell line lacking IRAK. In addition, we show for the first time that members of the IRAK family are indispensable elements of lipopolysaccharide signal transduction. The discovery of IRAK-M adds another level of complexity to our understanding of signaling by members of the Toll/IL-1 receptor family.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Antigens, Differentiation / metabolism
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Drosophila Proteins*
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Gene Library
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Humans
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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 / chemistry
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Protein Kinases / isolation & purification
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / chemistry
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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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Signal Transduction*
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TNF Receptor-Associated Factor 6
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Drosophila Proteins
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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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IRAK3 protein, human
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Interleukin-1 Receptor-Associated Kinases
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Protein Serine-Threonine Kinases