Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling

doi:10.1073/pnas.1701990114

	Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling
	Li, Lunyi 1,2; Guo, Xingdong 1,2; Shi, Xiaoshan 1,2; Li, Changting 1,2; Wu, Wei 1,2; Yan, Chengsong 1,2; Wang, Haopeng3 ; Li, Hua 1,2; Xu, Chenqi1,2,3
	2017-07-18
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN	0027-8424
卷号	114 期号:29 页码:E5891-E5899
发表状态	已发表
DOI	10.1073/pnas.1701990114
摘要	Antigen-triggered T-cell receptor (TCR) phosphorylation is the first signaling event in T cells to elicit adaptive immunity against invading pathogens and tumor cells. Despite its physiological importance, the underlying mechanism of TCR phosphorylation remains elusive. Here, we report a key mechanism regulating the initiation of TCR phosphorylation. The major TCR kinase Lck shows high selectivity on the four CD3 signaling proteins of TCR. CD3 epsilon is the only CD3 chain that can efficiently interact with Lck, mainly through the ionic interactions between CD3 epsilon basic residue-rich sequence (BRS) and acidic residues in the Unique domain of Lck. We applied a TCR reconstitution system to explicitly study the initiation of TCR phosphorylation. The ionic CD3 epsilon-Lck interaction controls the phosphorylation level of the whole TCR upon antigen stimulation. CD3 epsilon BRS is sequestered in the membrane, and antigen stimulation can unlock this motif. Dynamic opening of CD3 epsilon BRS and its subsequent recruitment of Lck thus can serve as an important switch of the initiation of TCR phosphorylation.
关键词	T-cell receptor Lck initial phosphorylation substrate selectivity ionic interaction
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收录类别	SCI
语种	英语
资助项目	NSFC[31470734]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000405662300018
出版者	NATL ACAD SCIENCES
WOS关键词	INDUCED CONFORMATIONAL-CHANGE ; CYTOPLASMIC DOMAIN ; MEMBRANE-BINDING ; TYROSINE KINASE ; IMMUNOLOGICAL SYNAPSE ; CANCER-IMMUNOTHERAPY ; SUBUNIT CONTAINS ; LCK ; TCR ; LIGAND
原始文献类型	Article
通讯作者	Xu, Chenqi
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/4530
专题	生命科学与技术学院_特聘教授组_许琛琦组生命科学与技术学院_PI研究组_王皞鹏组
通讯作者	Xu, Chenqi
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Chinese Acad Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab M, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Sci Res Ctr, Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Lunyi,Guo, Xingdong,Shi, Xiaoshan,et al. Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017,114(29):E5891-E5899.
APA	Li, Lunyi.,Guo, Xingdong.,Shi, Xiaoshan.,Li, Changting.,Wu, Wei.,...&Xu, Chenqi.(2017).Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,114(29),E5891-E5899.
MLA	Li, Lunyi,et al."Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114.29(2017):E5891-E5899.