The Unique Disulfide Bond-stabilized W1 beta 4-beta 1 Loop in the alpha(4)beta-Propeller Domain Regulates Integrin alpha(4)beta(7) Affinity and Signaling

	The Unique Disulfide Bond-stabilized W1 beta 4-beta 1 Loop in the alpha(4)beta-Propeller Domain Regulates Integrin alpha(4)beta(7) Affinity and Signaling
	Yue, J; Pan, YD; Sun, LF; Zhang, K; Liu, J; Lu, L; Chen, JF
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2013
卷号	288 期号:20 页码:14228-14237
通讯作者	Chen, JF (reprint author), Inst Biochem & Cell Biol, 320 YueYang Rd, Shanghai 200031, Peoples R China.,jfchen@sibcb.ac.cn
英文摘要	Integrin alpha(4)beta(7) mediates rolling and firm adhesion of lymphocytes pre- and post-activation, which is distinct from most integrins only mediating firm cell adhesion upon activation. This two-phase cell adhesion suggests a unique molecular basis for the dynamic interaction of alpha(4)beta(7) with its ligand, mucosal addressin cell adhesion molecule 1 (MAdCAM-1). Here we report that a disulfide bond-stabilized W1 beta 4-beta 1 loop in alpha(4) beta-propeller domain plays critical roles in regulating integrin alpha(4)beta(7) affinity and signaling. Either breaking the disulfide bond or deleting the disulfide bond-occluded segment in the W1 beta 4-beta 1 loop inhibited rolling cell adhesion supported by the low-affinity interaction between MAdCAM-1 and inactive alpha(4)beta(7) but negligibly affected firm cell adhesion supported by the high-affinity interaction between MAdCAM-1 and Mn2+-activated alpha(4)beta(7). Additionally, disrupting the disulfide bond or deleting the disulfide bond-occluded segment not only blocked the conformational change and activation of alpha(4)beta(7) triggered by talin or phorbol-12-myristate-13-acetate via inside-out signaling but also disrupted integrin-mediated outside-in signaling and impaired phosphorylation of focal adhesion kinase and paxillin. Thus, these findings reveal a particular molecular basis for alpha(4)beta(7)-mediated rolling cell adhesion and a novel regulatory element of integrin affinity and signaling.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	CRYSTAL-STRUCTURE ; DIVALENT-CATIONS ; BINDING-SITES ; FIRM ADHESION ; OUTSIDE-IN ; ACTIVATION ; DISTINCT ; SUBUNIT ; LIGAND ; LFA-1
收录类别	SCI
语种	英语
WOS记录号	WOS:000319253500027
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/463]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yue, J,Pan, YD,Sun, LF,et al. The Unique Disulfide Bond-stabilized W1 beta 4-beta 1 Loop in the alpha(4)beta-Propeller Domain Regulates Integrin alpha(4)beta(7) Affinity and Signaling[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(20):14228-14237.
APA	Yue, J.,Pan, YD.,Sun, LF.,Zhang, K.,Liu, J.,...&Chen, JF.(2013).The Unique Disulfide Bond-stabilized W1 beta 4-beta 1 Loop in the alpha(4)beta-Propeller Domain Regulates Integrin alpha(4)beta(7) Affinity and Signaling.JOURNAL OF BIOLOGICAL CHEMISTRY,288(20),14228-14237.
MLA	Yue, J,et al."The Unique Disulfide Bond-stabilized W1 beta 4-beta 1 Loop in the alpha(4)beta-Propeller Domain Regulates Integrin alpha(4)beta(7) Affinity and Signaling".JOURNAL OF BIOLOGICAL CHEMISTRY 288.20(2013):14228-14237.