Protein kinase D1: a new component in TLR9 signaling.

Protein kinase D1: a new component in TLR9 signaling.
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蛋白激酶D1:TLR9信号传导中的新组件。

DOI:
10.4049/jimmunol.181.3.2044
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发表时间:
2008-08-01
影响因子:
4.4
通讯作者:
Yi, Ae-Kyung
Yi, Ae-Kyung
中科院分区:
医学2区
文献类型:
--
作者:
Park, Jeoung-Eun;Kim, Young-In;Yi, Ae-Kyung

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蛋白激酶D_1(PKD_1)广泛表达,调节氧化应激、基因表达、细胞存活和囊泡运输等多种细胞过程。然而,单核细胞中PKD1的存在和功能目前尚不清楚。在此,我们提供了PKD1参与巨噬细胞Toll样受体(TLR)9信号转导的证据。B类CpG DNA(CpG-B DNA)通过依赖于巨噬细胞内膜pH、TLR9、MyD88和IRAK1的途径诱导PKD1的激活。在CpG-B DNA刺激下,PKD1与TLR9/MyD88/IRAK/TRAF6复合体相互作用。敲除PKD1后发现,PKD1是激活NF-κB和MAPKs,以及随后表达细胞因子以响应CpG-BDNA所必需的。我们的研究结果表明,PKD1在TLR9介导的巨噬细胞活化中是一个关键的信号调节器。
Protein kinase D1 (PKD1) is expressed ubiquitously and regulate diverse cellular processes such as oxidative stress, gene expression, cell survival, and vesicle trafficking. However, the presence and function of PKD1 in monocytic cells are currently unknown. Here we provide evidence that PKD1 is involved in Toll-like receptor (TLR) 9 signaling in macrophages. Class B type CpG DNA (CpG-B DNA) induced activation of PKD1 via a pathway that is dependent on endosomal pH, TLR9, MyD88, and IRAK1 in macrophages. Upon CpG-B DNA stimulation, PKD1 interacted with the TLR9/MyD88/IRAK/TRAF6 complex. Knockdown of PKD1 revealed that PKD1 is required for activation of NF-κB and MAPKs, and subsequent expression of cytokines in response to CpG-B DNA. Our findings identify PKD1 as a key signaling modulator in TLR9-mediated macrophage activation.
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