| IRAK-4-dependent degradation of IRAK-1 is a negative feedback signal for TLR-mediated NF-kappaB activation. | |
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MedLine Citation:
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PMID: 18079163 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The activation of interleukin 1 receptor-associated kinase (IRAK)-1 is a key event in the transmission of signals from Toll-like receptors (TLRs). The catalytic activity of the protein kinase is not essential for its ability to activate nuclear factor (NF) kappaB, because transfection of a kinase-dead mutant of IRAK-1 (IRAK-1KD) is able to activate NF-kappaB in HEK293T cells. In the present study, we observed that the effect of IRAK-1KD was impaired by simultaneous expression of IRAK-4. The effect of IRAK-4 was accompanied by the phosphorylation and degradation of IRAK-1KD. Expression of IRAK-4KD instead of IRAK-4 did not cause these events. In IRAK-4-deficient Raw264.7 macrophages that were prepared by introducing short-hairpin RNA probes, the basal level of IRAK-1 was increased markedly. Stimulation of these cells with TLR ligands did not cause the degradation of IRAK-1, which was clearly observed in the parent cells. These results suggested that the expression of IRAK-4 alone is sufficient to cause the degradation of IRAK-1; the autophosphorylation of IRAK-1 is not necessary to terminate the TLR-induced activation of NF-kappaB. IRAK-4 has an ability to induce the degradation of IRAK-1 in addition to its role as an activator of IRAK-1. |
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Authors:
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Miho Kubo-Murai; Kaoru Hazeki; Kiyomi Nigorikawa; Takatoshi Omoto; Norimitsu Inoue; Osamu Hazeki |
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Publication Detail:
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Type: Journal Article Date: 2007-12-13 |
Journal Detail:
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Title: Journal of biochemistry Volume: 143 ISSN: 0021-924X ISO Abbreviation: J. Biochem. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-03 Completed Date: 2008-06-23 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0376600 Medline TA: J Biochem Country: Japan |
Other Details:
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Languages: eng Pagination: 295-302 Citation Subset: IM |
Affiliation:
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Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Feedback, Physiological* / drug effects Humans I-kappa B Proteins / metabolism Interleukin-1 Receptor-Associated Kinases / metabolism* Lipopolysaccharides / pharmacology Macrophages / drug effects, metabolism Mice NF-kappa B / metabolism* Protein Processing, Post-Translational* / drug effects Signal Transduction* / drug effects Toll-Like Receptor 4 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/I-kappa B Proteins; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Toll-Like Receptor 4; EC 2.7.1.37/IRAK1 protein, human; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases |
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