蛋白激酶Cδ结合TIRAP/Mal以参与Toll样受体信号传导。
Protein kinase Cdelta binds TIRAP/Mal to participate in TLR signaling.
作者信息
Kubo-Murai Miho, Hazeki Kaoru, Sukenobu Naoe, Yoshikawa Kyoko, Nigorikawa Kiyomi, Inoue Kazumi, Yamamoto Toshiyoshi, Matsumoto Misako, Seya Tsukasa, Inoue Norimitsu, Hazeki Osamu
机构信息
The Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
出版信息
Mol Immunol. 2007 Mar;44(9):2257-64. doi: 10.1016/j.molimm.2006.11.005. Epub 2006 Dec 11.
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 Cdelta (PKCdelta). TIRAP/Mal GST-fusion protein and a TIRAP/Mal antibody were able to precipitate PKCdelta 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 IkappaB in RAW264.7 cells were abolished by depletion of PKCdelta. These results suggest that PKCdelta binding to TIRAP/Mal promotes TLR signaling events.
Toll样受体（TLR）家族成员识别病原体中的特定分子模式。通过TLR发出的信号会引发一个近端事件，该事件涉及衔接蛋白与受体的直接结合。我们观察到，作为TLR2和TLR4的衔接蛋白，TIRAP/Mal可与蛋白激酶Cδ（PKCδ）结合。TIRAP/Mal GST融合蛋白和TIRAP/Mal抗体能够从大鼠腹腔巨噬细胞和THP1细胞裂解物中沉淀出PKCδ。TIRAP/Mal的截短突变体表明，TIRAP/Mal的TIR结构域负责这种结合。在RAW264.7细胞中，PKCδ的缺失消除了TLR2和TLR4介导的p38 MAPK、IKK和IkappaB的磷酸化。这些结果表明，PKCδ与TIRAP/Mal的结合促进了TLR信号事件。
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