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	SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production
	An, Huazhang ; Zhao, Wei ; Hou, Jin ; Zhang, Yan ; Xie, Yun ; Zheng, Yuejuan ; Xu, Hongmei ; Qian, Cheng ; Zhou, Jun ; Yu, Yizhi ; Liu, Shuxun ; Feng, Gensheng ; Cao, Xuetao
	2010-05-11 ; 2010-05-11
关键词	TOLL-LIKE RECEPTORS NF-KAPPA-B TYROSINE-PHOSPHATASE SIGNALING PATHWAY INTERLEUKIN-1 RECEPTOR SH2 DOMAIN LIPOPOLYSACCHARIDE INDUCTION BETA CELL Immunology
中文摘要	The Toll-like receptor 3 (TLR3) and TLR4-signaling pathway that involves the adaptor protein TRIF activates type I interferon (IFN) and proinflammatory cytokine expression. Little is known about how TRIF pathway-dependent gene expression is regulated. SH2-containing protein tyrosine phosphatase 2 (SHP-2) is a widely expressed cytoplasmic tyrosine phosphatase. Here we demonstrate that SHP-2 negatively regulated TLR4- and TLR3-activated IFN-beta production. SHP-2 inhibited TLR3-activated but not TLR2-, TLR7-, and TLR9-activated proinflammatory cytokine IL-6 and TNF-alpha production. SHP-2 inhibited poly(I:C)-induced cytokine production by a phosphatase activity-independent mechanism. C-terminal domain of SHP-2 directly bound TANK binding kinase (TBK1) by interacting with the kinase domain of TBK1. SHP-2 deficiency increased TBK1-activated IFN-beta and TNF-alpha expression. TBK1 knockdown inhibited poly(I:C)-induced IL-6 production in SHP-2-deficient cells. SHP-2 also inhibited poly(I:C)-induced activation of MAP kinase pathways. These results demonstrate that SHP-2 specifically negatively regulate TRIF-mediated gene expression in TLR signaling, partially through inhibiting TBK1-activated signal transduction.
语种	英语 ; 英语
出版者	CELL PRESS ; CAMBRIDGE ; 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/27546]
专题	清华大学
推荐引用方式 GB/T 7714	An, Huazhang,Zhao, Wei,Hou, Jin,et al. SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production[J],2010, 2010.
APA	An, Huazhang.,Zhao, Wei.,Hou, Jin.,Zhang, Yan.,Xie, Yun.,...&Cao, Xuetao.(2010).SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production..
MLA	An, Huazhang,et al."SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production".(2010).

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