JNK2 and IKKβ are required for activating the innate response to viral infection
JNK2 and IKKβ are required for activating the innate response to viral infection
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DOI：
10.1016/s1074-7613(00)80146-6
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发表时间：
1999-12-01
期刊：
影响因子：
32.4
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Chu, WM;Ostertag, D;Karin, M
病毒感染或双链（ds）RNA诱导干扰素（IFN）和其他细胞因子。介导IFN诱导的转录因子是已知的，但调节它们的信号通路不太清楚。我们现在描述两个这样的途径。导致NF-κ B的第一条途径依赖于dsRNA反应性蛋白激酶（PKR），PKR又通过IKK β亚基激活I κ B激酶（IKK）。第二种病毒和dsRNA应答途径是PKR独立的，并且涉及Jun激酶（JNK）激活，导致AP-1的刺激。IKK β和JNK 2两者对于响应病毒感染或dsRNA有效诱导I型IFN和其它细胞因子是必需的。本研究确立了这些激酶在先天免疫应答激活中的一般作用。
Viral infection or double-stranded (ds) RNA induce interferons (IFN) and other cytokines. Transcription factors mediating IFN induction are known, but the signaling pathways that regulate them are less clear. We now describe two such pathways. The first pathway leading to NF-kappa B depends on the dsRNA-responsive protein kinase (PKR), which in turn activates I kappa B kinase (IKK) through the IKK beta subunit. The second viral- and dsRNA-responsive pathway is PKR independent and involves Jun kinase (JNK) activation leading to stimulation of AP-1. Both IKK beta and JNK2 are essential for efficient induction of type I IFN and other cytokines in response to viral infection or dsRNA. This study establishes a general role for these kinases in activation of innate immune responses.