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PMID:15292196
| Citation |
Lye, E, Mirtsos, C, Suzuki, N, Suzuki, S and Yeh, WC (2004) The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling. J. Biol. Chem. 279:40653-8 |
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| Abstract |
Interleukin 1 receptor (IL-1R)-associated kinase-4 (IRAK-4) is required for various responses induced by IL-1R and Toll-like receptor signals. However, the molecular mechanism of IRAK-4 signaling and the role of its kinase activity have remained elusive. In this report, we demonstrate that IRAK-4 is recruited to the IL-1R complex upon IL-1 stimulation and is required for the recruitment of IRAK-1 and its subsequent activation/degradation. By reconstituting IRAK-4-deficient cells with wild type or kinase-inactive IRAK-4, we show that the kinase activity of IRAK-4 is required for the optimal transduction of IL-1-induced signals, including the activation of IRAK-1, NF-kappaB, and JNK, and the maximal induction of inflammatory cytokines. Interestingly, we also discover that the IRAK-4 kinase-inactive mutant is still capable of mediating some signals. These results suggest that IRAK-4 is an integral part of the IL-1R signaling cascade and is capable of transmitting signals both dependent on and independent of its kinase activity. |
| Links |
PubMed Online version:10.1074/jbc.M402666200 |
| Keywords |
Animals; Blotting, Western; Cell Line; Cloning, Molecular; Cytokines/metabolism; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Genes, Reporter; Genetic Vectors; Humans; Interleukin-1/metabolism; Interleukin-1 Receptor-Associated Kinases; JNK Mitogen-Activated Protein Kinases; Luciferases/metabolism; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases/metabolism; Mutation; NF-kappa B/metabolism; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor)/metabolism; Phosphotransferases (Alcohol Group Acceptor)/physiology; Precipitin Tests; Protein Structure, Tertiary; Recombinant Proteins/chemistry; Signal Transduction; Transfection; Transgenes |
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Significance
Annotations
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