Skip Navigation



Journal of Biochemistry Advance Access published online on December 13, 2007
Journal of Biochemistry, doi:10.1093/jb/mvm234
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
143/3/295    most recent
mvm234v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Kubo-Murai, M.
Right arrow Articles by Hazeki, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kubo-Murai, M.
Right arrow Articles by Hazeki, O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Japanese Biochemical Society

IRAK-4-dependent Degradation of IRAK-1 is a Negative Feedback Signal for TLR-mediated NF-{kappa}B Activation

Miho Kubo-Murai1, Kaoru Hazeki1,*, Kiyomi Nigorikawa1, Takatoshi Omoto1, Norimitsu Inoue2 and Osamu Hazeki1

1 Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
2 Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan

*To whom correspondence should be addressed: Dr. Hazeki, Kaoru, Tel: +81-82-257-5308, Fax: +81-82-257-5309, e-mail: khazeki{at}hiroshima-u.ac.jp

Received August 20, 2007; Accepted November 3, 2007


  Abstract

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) {kappa}B, because transfection of a kinase-dead mutant of IRAK-1 (IRAK-1KD) is able to activate NF-{kappa}B 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-{kappa}B. IRAK-4 has an ability to induce the degradation of IRAK-1 in addition to its role as an activator of IRAK-1.

Key Words: IRAK, LPS, NF-{kappa}B, Phosphorylation, TLR


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.