Abstract
The Toll/interleukin-1 receptor (TIR) family members play important roles in host defense. These receptors signal through TIR domain-containing adapter proteins. In this report, we identified a novel TIR domain-containing adapter protein designated as TIRP. Co-immunoprecipitation experiments suggest that TIRP is associated with IL-1 receptors. TIRP also interacts with kinase-inactive mutants of IRAK and IRAK-4, IRAK-2, IRAK-M, and TRAF6. Overexpression of TIRP activates NF-kappaB and potentiates IL-1 receptor-mediated NF-kappaB activation. A dominant negative mutant of TIRP inhibits IL-1- but not tumor necrosis factor-triggered NF-kappaB activation. Moreover, TIRP-mediated NF-kappaB activation is inhibited by dominant negative mutants of IRAK, IRAK-2, TRAF6, and IKKbeta. Our findings suggest that TIRP is involved in IL-1-triggered NF-kappaB activation and functions upstream of IRAK, IRAK-2, TRAF6, and IKKbeta
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport / genetics
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Adaptor Proteins, Vesicular Transport / physiology*
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Amino Acid Sequence
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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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Membrane Glycoproteins / genetics*
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Molecular Sequence Data
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Mutation
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Protein Kinases / physiology
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Protein Structure, Tertiary / genetics
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Receptors, Cell Surface / genetics*
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Receptors, Interleukin / genetics
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Receptors, Interleukin / physiology*
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Receptors, Interleukin-1 / genetics*
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Sequence Alignment
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Signal Transduction
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Toll-Like Receptors
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Interleukin-1
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-1
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TICAM2 protein, human
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Ticam2 protein, mouse
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Toll-Like Receptors
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Protein Kinases
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IRAK3 protein, human
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Interleukin-1 Receptor-Associated Kinases
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Irak3 protein, mouse