标题：Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM
作者：Huai, Wanwan;Song, Hui;Wang, Lijuan;Li, Bingqing;Zhao, Jing;Han, Lihui;Gao, Chengjiang;Jiang, Guosheng;Zhang, Lining;Zhao, Wei
作者机构：[Huai, W] Department of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China;[ Song, H] Department of 更多
通讯作者地址：[Zhao, W]Shandong Univ, Sch Med, Dept Immunol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：The Journal of Immunology: Official Journal of the American Association of Immunologists
摘要：TLR4 recruits TRIF-related adaptor molecule (TRAM, also known as TICAM2) as a sorting adaptor to facilitate the interaction between TLR4 and TRIF and then initiate TRIF-dependent IRF3 activation. However, the mechanisms by which TRAM links downstream molecules are not fully elucidated. In this study, we show that TRAM undergoes tyrosine phosphorylation upon TLR4 activation and that is required for TLR4-induced IRF3 activation. Protein tyrosine phosphatase nonreceptor type 4 (PTPN4), a protein tyrosine phosphatase, inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRAM, resulting in the disturbance of TRAM-TRIF interaction. Consequently, PTPN4 specifically inhibits TRIF-dependent IRF3 activation and IFN-beta production in TLR4 pathway. Therefore, our results provide new insight into the TLR4 pathway and identify PTPN4 as a specific inhibitor of TRIF-dependent TLR4 pathway. Targeting PTPN4 would be beneficial for the development of new strategy to control TLR4-associated diseases without unwanted side effects.