Abstract
The signaling pathway downstream of the mammalian interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) is evolutionally conserved with that mediated by the Drosophila Toll protein. Toll initiates its signal through the adapter molecule Tube and the serine-threonine kinase Pelle. Pelle is highly homologous to members of the IL-1R-associated kinase (IRAK) family in mammals. Recently, a novel Pelle-interacting protein called Pellino was identified in Drosophila. We now report a mammalian counterpart of Pellino, termed Pellino 1, which is required for NF kappa B activation and IL-8 gene expression in response to IL-1, probably through its signal-dependent interaction with IRAK4, IRAK, and the tumor necrosis factor receptor-associated factor 6 (TRAF6). The Pellino 1-IRAK-IRAK4-TRAF6 signaling complex is likely to be intermediate, located between the IL-1 receptor complex and the TAK1 complex in the IL-1 pathway.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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DNA, Complementary
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Gene Expression Regulation / physiology
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Humans
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Interleukin-1 / physiology*
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Interleukin-1 Receptor-Associated Kinases
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Interleukin-8 / genetics
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Molecular Sequence Data
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NF-kappa B / metabolism
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Precipitin Tests
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Proteins / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism*
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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TNF Receptor-Associated Factor 6
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Ubiquitin-Protein Ligases
Substances
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DNA, Complementary
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Interleukin-1
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Interleukin-8
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NF-kappa B
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Nuclear Proteins
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Proteins
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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TNF Receptor-Associated Factor 6
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PELI1 protein, human
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Ubiquitin-Protein Ligases
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Phosphotransferases (Alcohol Group Acceptor)
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IRAK4 protein, human
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Interleukin-1 Receptor-Associated Kinases