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学科主题: 基础医学
题名:
Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT
作者: Kang, Qiaozhen1; Yu, Yu1; Pei, Xinhong1; Hughes, Richard1; Heck, Susanne; Zhang, Xihui1; Guo, Xinhua1; Halverson, Gregory; Mohandas, Narla1; An, Xiuli1,2
刊名: BLOOD
发表日期: 2009-06-11
DOI: 10.1182/blood-2008-10-182329
卷: 113, 期:24, 页:6128-6137
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology
研究领域[WOS]: Hematology
关键词[WOS]: MEMBRANE SKELETON ; ANTIGEN RECEPTOR ; ERM PROTEINS ; FUNCTIONAL-CHARACTERIZATION ; IMMUNOLOGICAL SYNAPSE ; SIGNAL-TRANSDUCTION ; TYROSINE KINASES ; TUMOR-SUPPRESSOR ; LINKER EZRIN ; FERM DOMAIN
英文摘要:

Protein 4.1R (4.1R) was first identified in red cells where it plays an important role in maintaining mechanical stability of red cell membrane. 4.1R has also been shown to be expressed in T cells, but its function has been unclear. In the present study, we use 4.1R-deficient mice to explore the role of 4.1R in T cells. We show that 4.1R is recruited to the immunologic synapse after T cell-antigen receptor (TCR) stimulation. We show further that CD4(+) T cells of 4.1R(-/)-mice are hyperactivated and that they displayed hyperproliferation and increased production of interleukin-2 (IL-2) and interferon gamma (IFN gamma). The hyperactivation results from enhanced phosphorylation of LAT and its downstream signaling molecule ERK. The 4.1R exerts its effect by binding directly to LAT, and thereby inhibiting its phosphorylation by ZAP-70. Moreover, mice deficient in 4.1R display an elevated humoral response to immunization with T cell-dependent antigen. Thus, we have defined a hitherto unrecognized role for 4.1R in negatively regulating T-cell activation by modulating intracellular signal transduction. (Blood. 2009; 113: 6128-6137)

语种: 英语
所属项目编号: DK 26263 ; DK 32094 ; HL31579
项目资助者: National Institutes of Health (Bethesda, MD) ; MetLife Foundation (New York, NY)
WOS记录号: WOS:000267147100017
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66751
Appears in Collections:基础医学院_生物物理学系_期刊论文

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作者单位: 1.New York Blood Ctr, Red Cell Physiol Lab, New York, NY 10065 USA
2.Peking Univ, Dept Biophys, Hlth Sci Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Kang, Qiaozhen,Yu, Yu,Pei, Xinhong,et al. Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT[J]. BLOOD,2009,113(24):6128-6137.
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