IRAK-M mediates Toll-like receptor/IL-1R-induced NF kappa B activation   and cytokine production

doi:10.1038/emboj.2013.2

CORC > 北京大学 > 生命科学学院

	IRAK-M mediates Toll-like receptor/IL-1R-induced NF kappa B activation and cytokine production
	Zhou, Hao ; Yu, Minjia ; Fukuda, Koichi ; Im, Jinteak ; Yao, Peng ; Cui, Wei ; Bulek, Katarzyna ; Zepp, Jarod ; Wan, Youzhong ; Kim, Tae Whan ; Yin, Weiguo ; Ma, Victoria ; Thomas, James ; Gu, Jun ; Wang, Jian-an ; DiCorleto, Paul E. ; Fox, Paul L. ; Qin, Jun ; Li, Xiaoxia
刊名	embo journal
	2013
关键词	IRAK myddosome signalling Toll-like receptor INTERLEUKIN-1 RECEPTOR KINASE-ACTIVITY POSTTRANSCRIPTIONAL CONTROL DROSOPHILA TOLL FAMILY COMPLEX MEMBER IMMUNITY MYD88 MNK1
DOI	10.1038/emboj.2013.2
英文摘要	Toll-like receptors transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK-1, 2, M and 4). IRAK-1 and IRAK-2, known to form Myddosomes with MyD88-IRAK-4, mediate TLR7-induced TAK1-dependent NF kappa B activation. IRAK-M was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signalling. However, we now found that IRAK-M was also able to interact with MyD88-IRAK-4 to form IRAK-M Myddosome to mediate TLR7-induced MEKK3-dependent second wave NF kappa B activation, which is uncoupled from post-transcriptional regulation. As a result, the IRAK-M-dependent pathway only induced expression of genes that are not regulated at the post-transcriptional levels (including inhibitory molecules SOCS1, SHIP1, A20 and I kappa B alpha), exerting an overall inhibitory effect on inflammatory response. On the other hand, through interaction with IRAK-2, IRAK-M inhibited TLR7-mediated production of cytokines and chemokines at translational levels. Taken together, IRAK-M mediates TLR7-induced MEKK3-dependent second wave NF kappa B activation to produce inhibitory molecules as a negative feedback for the pathway, while exerting inhibitory effect on translational control of cytokines and chemokines. The EMBO Journal (2013) 32, 583-596. doi: 10.1038/emboj.2013.2; Published online 1 February 2013; Biochemistry & Molecular Biology; Cell Biology; SCI(E); 17; ARTICLE; 4; 583-596; 32
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/391968]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhou, Hao,Yu, Minjia,Fukuda, Koichi,et al. IRAK-M mediates Toll-like receptor/IL-1R-induced NF kappa B activation and cytokine production[J]. embo journal,2013.
APA	Zhou, Hao.,Yu, Minjia.,Fukuda, Koichi.,Im, Jinteak.,Yao, Peng.,...&Li, Xiaoxia.(2013).IRAK-M mediates Toll-like receptor/IL-1R-induced NF kappa B activation and cytokine production.embo journal.
MLA	Zhou, Hao,et al."IRAK-M mediates Toll-like receptor/IL-1R-induced NF kappa B activation and cytokine production".embo journal (2013).