The TAK1-JNK cascade is required for IRF3 function in the innate immune response

	The TAK1-JNK cascade is required for IRF3 function in the innate immune response
	Zhang, BH; Li, M; Chen, L; Yang, K; Shan, YF; Zhu, LH; Sun, SG; Li, L; Wang, C
刊名	CELL RESEARCH
	2009
卷号	19 期号:4 页码:412-428
关键词	JNK TAK1 IRF3 innate immunity
通讯作者	Wang, C (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,lli@sibs.ac.cn ; cwang01@sibs.ac.cn
英文摘要	Interferon regulatory factor (IRF)3 is critical for the transcriptional induction of chemokines and cytokines during viral or bacterial invasion. The kinases Tank binding kinase (TBK)1 and Ikappa B kinase (IKK)epsilon can phosphorylate the C-terminal part of IRF3 and play important roles in IRF3 activation. In this study, we show that another kinase, c-Jun-NH(2)-terminal kinase (JNK), phosphorylates IRF3 on its N-terminal serine 173 residue, and TAK1 can stimulate IRF3 phosphorylation via JNK. JNK specific inhibitor SP600125 inhibits the N-terminal phosphorylation without affecting the C-terminal phosphorylation. In addition, IRF3-mediated gene expressions on lipopolysaccharide (LPS) or polyinosinic-cytidylic acid (polyI:C) treatment are severely impaired by SP600125, as well as for reporter gene assay of IRF3 activation. Knockdown of TAK1 further confirmed these observations. Interestingly, constitutive active IRF3(5D) can be inhibited by SP600125; JNK1 can synergize the action of IRF3(5D), but not the S173A-IRF3( 5D) mutant. More importantly, polyI: C failed to induce the phosphorylation of mutant S173A and SP600125 dramatically abrogated IRF3 phosphorylation and dimerization that was stimulated by polyI: C. Thus, this study demonstrates that the TAK1-JNK cascade is required for IRF3 function, in addition to TBK1/IKK epsilon, uncovering a new mechanism for mitogen-activated protein (MAP) kinase to regulate the innate immunity.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	INTERFERON REGULATORY FACTOR-3 ; NF-KAPPA-B ; DOUBLE-STRANDED-RNA ; TOLL-LIKE RECEPTORS ; PROTEIN-KINASE-C ; SIGNAL-TRANSDUCTION ; ANTIVIRAL RESPONSE ; TERMINAL KINASE ; ADAPTER MOLECULE ; CUTTING EDGE
收录类别	SCI
语种	英语
WOS记录号	WOS:000265700100004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1178]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, BH,Li, M,Chen, L,et al. The TAK1-JNK cascade is required for IRF3 function in the innate immune response[J]. CELL RESEARCH,2009,19(4):412-428.
APA	Zhang, BH.,Li, M.,Chen, L.,Yang, K.,Shan, YF.,...&Wang, C.(2009).The TAK1-JNK cascade is required for IRF3 function in the innate immune response.CELL RESEARCH,19(4),412-428.
MLA	Zhang, BH,et al."The TAK1-JNK cascade is required for IRF3 function in the innate immune response".CELL RESEARCH 19.4(2009):412-428.