Protein kinase Cδ binds TIRAP/Mal to participate in TLR signaling

被引:42
作者
Kubo-Murai, Miho
Hazeki, Kaoru [1 ]
Sukenobu, Naoe
Yoshikawa, Kyoko
Nigorikawa, Kiyomi
Inoue, Kazumi
Yamamoto, Toshiyoshi
Matsumoto, Misako
Seya, Tsukasa
Inoue, Norimitsu
Hazeki, Osamu
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Div Mol Med Sci, Minami Ku, Hiroshima 7348551, Japan
[2] Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan
[3] Hokkaido Univ, Grad Sch Med, Dept Microbiol & Immunol, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[4] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Immunol, Higashinari Ku, Osaka 5378511, Japan
关键词
PKC delta; TLR; macrophage; signal transduction;
D O I
10.1016/j.molimm.2006.11.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Toll-like receptor (TLR) family members recognize specific molecular patterns within pathogens. Signaling through TLRs results in a proximal event that involves direct binding of adaptor proteins to the receptors. We observed that TIRAP/Mal, an adaptor protein for TLR2 and TLR4, binds protein kinase C delta (PKC delta). TIRAP/Mal GST-fusion protein and a TIRAP/Mal antibody were able to precipitate PKC delta from rat peritoneal macrophage and THP1 cell lysates. Truncation mutants of TIRAP/Mal showed that the TIR domain of TIRAP/Mal is responsible for binding. TLR2- and TLR4-mediated phosphorylation of p38 MAPK, IKK, and IKB in RAW264.7 cells were abolished by depletion of PKC delta. These results suggest that PKC delta binding to TIRAP/Mal promotes TLR signaling events. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2257 / 2264
页数:8
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