The E3 ligases Itch and WWP2 cooperate to limit T(H)2 differentiation by enhancing signaling through the TCR
文献类型:期刊论文
作者 | Aki, Daisuke1,2; Li, Hui1; Zhang, Wen1; Zheng, Mingke1; Liu, Yun-Cai1,2; Elly, Chris2; Lee, Jee H.2; Zou, Weiguo3 |
刊名 | NATURE IMMUNOLOGY |
出版日期 | 2018 |
卷号 | 19期号:7页码:766-+ |
ISSN号 | 1529-2908 |
关键词 | Cd4(+) T-cells Ubiquitin Ligases Immune-response Moth-eaten Cbl-b Activation Protein Degradation Shp-1 Ubiquitylation |
DOI | 10.1038/541590-018-0137-8 |
文献子类 | Article |
英文摘要 | The mechanisms by which the sensitivity of naive CD4(+) T cells to stimulation by the cognate antigen via the T cell antigen receptor (TCR) determines their differentiation into distinct helper T cell subsets remain elusive. Here we demonstrate functional collaboration of the ubiquitin E3 ligases Itch and WWP2 in regulating the strength of the TCR signal. Mice lacking both Itch and WWP2 in T cells showed spontaneous autoimmunity and lung inflammation. CD4(+) T cells deficient in Itch and WWP2 exhibited hypo-responsiveness to TCR stimulation and a bias toward differentiation into the T(H)2 subset of helper T cells. Itch and WWP2 formed a complex and cooperated to enhance TCR-proximal signaling by catalyzing the conjugation of atypical ubiquitin chains to the phosphatase SHP-1 and reducing the association of SHP-1 with the tyrosine kinase Lck. These findings indicate that targeted ubiquitination regulates the strength of the TCR signal and differentiation toward the T(H)2 lineage. |
电子版国际标准刊号 | 1529-2916 |
WOS研究方向 | Immunology |
语种 | 英语 |
WOS记录号 | WOS:000436341300021 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3495] |
专题 | 生化所2018年发文 上海生化细胞研究所_上海生科院生化细胞研究所 |
通讯作者 | Liu, Yun-Cai |
作者单位 | 1.Tsinghua Univ, Inst Immunol, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China; 2.La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA; 3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Aki, Daisuke,Li, Hui,Zhang, Wen,et al. The E3 ligases Itch and WWP2 cooperate to limit T(H)2 differentiation by enhancing signaling through the TCR[J]. NATURE IMMUNOLOGY,2018,19(7):766-+. |
APA | Aki, Daisuke.,Li, Hui.,Zhang, Wen.,Zheng, Mingke.,Liu, Yun-Cai.,...&Zou, Weiguo.(2018).The E3 ligases Itch and WWP2 cooperate to limit T(H)2 differentiation by enhancing signaling through the TCR.NATURE IMMUNOLOGY,19(7),766-+. |
MLA | Aki, Daisuke,et al."The E3 ligases Itch and WWP2 cooperate to limit T(H)2 differentiation by enhancing signaling through the TCR".NATURE IMMUNOLOGY 19.7(2018):766-+. |
入库方式: OAI收割
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