Modulation of tumor necrosis factor and interleukin-1-dependent NF-κB activity by mPLK IRAK
Modulation of tumor necrosis factor and interleukin-1-dependent NF-κB activity by mPLK IRAK
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DOI：
10.1074/jbc.274.19.13077
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发表时间：
1999-05-07
影响因子：
4.8
通讯作者：
Harrington, MA
中科院分区：
文献类型：
--
作者：
Vig, E;Green, M;Harrington, MA
固有免疫应答是抵御病原体的重要防御机制。这种应答的一个组成部分是核因子-κB（NF -κB）依赖的基因激活，这些基因编码炎症细胞因子如白细胞介素 - 8（IL - 8）以及细胞黏附分子如E - 选择素。丝氨酸/苏氨酸固有免疫激酶蛋白家族的成员被认为可介导固有免疫应答。丝氨酸/苏氨酸固有免疫激酶家族的一个成员，小鼠佩勒样激酶/人白细胞介素 - 1受体相关激酶（mPLK/IRAK），被认为在促进白细胞介素 - 1介导的炎症中起关键作用。然而，目前尚不清楚白细胞介素 - 1依赖的核因子 - κB激活是否需要mPLK/IRAK的催化活性。本研究表明，白细胞介素 - 1介导的核因子 - κB依赖信号的激活不需要mPLK/IRAK的催化活性。有趣的是，无催化活性的mPLK/IRAK抑制1型肿瘤坏死因子（TNF）受体依赖的核因子 - κB激活。mPLK/IRAK介导这种TNF反应的途径不依赖TRADD和TRAF2。我们的数据表明，除了在白细胞介素 - 1信号传导中的作用外，mPLK/IRAK还是一种新的信号转导途径的组成部分，通过该途径TNF R1激活核因子 - κB依赖的基因表达。
The innate immune response is an important defense against pathogenic agents. A component of this response is the NF-kappa B-dependent activation of genes encoding inflammatory cytokines such as interleukin-8 (IL-8) and cell adhesion molecules like E-selectin. Members of the serine/threonine innate immune kinase family of proteins have been proposed to mediate the innate immune response. One serine/threonine innate immune kinase family member, the mouse Pelle-like kinase/human interleukin-l receptor-associated kinase (mPLK/IRAK), has been proposed to play an obligate role in promoting IL-l-mediated inflammation. However, it is currently unknown whether mPLK/IRAK catalytic activity is required for IL-l-dependent NF-kappa B activation. The present study demonstrates that mPLK/IRAK catalytic activity is not required for IL-l-mediated activation of an NF-kappa B-dependent signal. Intriguingly, catalytically inactive mPLK/IRAK inhibits type 1 tumor necrosis factor (TNF) receptor-dependent NF-kappa B activation, The pathway through which mPLK/IRAK mediates this TNF response is TRADD- and TRAF2-independent. Our data suggest that in addition to its role in IL-1 signaling, mPLK/IRAK is a component of a novel signal transduction pathway through which TNF R1 activates NF-kappa B-dependent gene expression.