共 39 条
SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production
被引:243
作者:

An, Huazhang
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Zhao, Wei
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Hou, Jin
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Zhang, Yan
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Xie, Yun
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Zheng, Yuejuan
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Xu, Hongmei
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Qian, Cheng
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Zhou, Jun
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Yu, Yizhi
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Liu, Shuxun
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Feng, Gensheng
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机构: Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

Cao, Xuetao
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机构:
Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
机构:
[1] Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China
[2] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China
[3] Tsinghua Univ, Sch Med, Inst Immunol, Beijing 100084, Peoples R China
[4] Zhejiang Univ, Inst Immunol, Hangzhou 310031, Peoples R China
[5] Burnham Inst Med Res, La Jolla, CA 92037 USA
来源:
基金:
中国国家自然科学基金;
关键词:
D O I:
10.1016/j.immuni.2006.10.014
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
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.
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页码:919 / 928
页数:10
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