IR@PKUHSC  > 北京大学基础医学院  > 生物物理学系
学科主题基础医学
Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT
Kang, Qiaozhen1; Yu, Yu1; Pei, Xinhong1; Hughes, Richard1; Heck, Susanne; Zhang, Xihui1; Guo, Xinhua1; Halverson, Gregory; Mohandas, Narla1; An, Xiuli1,2
刊名BLOOD
2009-06-11
DOI10.1182/blood-2008-10-182329
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
WOS记录号WOS:000267147100017
项目编号DK 26263 ; DK 32094 ; HL31579
资助机构National Institutes of Health (Bethesda, MD) ; MetLife Foundation (New York, NY)
引用统计
被引频次:21[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66751
专题北京大学基础医学院_生物物理学系
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
推荐引用方式
GB/T 7714
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.
APA Kang, Qiaozhen.,Yu, Yu.,Pei, Xinhong.,Hughes, Richard.,Heck, Susanne.,...&An, Xiuli.(2009).Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT.BLOOD,113(24),6128-6137.
MLA Kang, Qiaozhen,et al."Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT".BLOOD 113.24(2009):6128-6137.
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