A PLC beta/PI3K gamma-GSK3 Signaling Pathway Regulates Cofilin Phosphatase Slingshot2 and Neutrophil Polarization and Chemotaxis

	A PLC beta/PI3K gamma-GSK3 Signaling Pathway Regulates Cofilin Phosphatase Slingshot2 and Neutrophil Polarization and Chemotaxis
	Tang, WW; Zhang, Y; Xu, WW; Harden, TK; Sondek, J; Sun, L; Li, L; Wu, DQ
刊名	DEVELOPMENTAL CELL
	2011
卷号	21 期号:6 页码:1038-1050
通讯作者	Wu, DQ (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.,dan.wu@yale.edu
英文摘要	Neutrophils, in response to a chemoattractant gradient, undergo dynamic F-actin remodeling, a process important for their directional migration or chemotaxis. However, signaling mechanisms for chemoattractants to regulate the process are incompletely understood. Here, we characterized chemoattractant-activated signaling mechanisms that regulate cofilin dephosphorylation and actin cytoskeleton reorganization and are critical for neutrophil polarization and chemotaxis. In neutrophils, chemoattractants induced phosphorylation and inhibition of GSK3 via both PLC beta-PKC and PI3K gamma-AKT pathways, leading to the attenuation of GSK3-mediated phosphorylation and inhibition of the cofilin phosphatase slingshot2 and an increase in dephosphorylated, active cofilin. The relative contribution of this GSK3-mediated pathway to neutrophil chemotaxis regulation depended on neutrophil polarity preset by integrin-induced polarization of PIP5K1C. Therefore, our study characterizes a signaling mechanism for chemoattractant-induced actin cytoskeleton remodeling and elucidates its context-dependent role in regulating neutrophil polarization and chemotaxis.
学科主题	Cell Biology; Developmental Biology
类目[WOS]	Cell Biology ; Developmental Biology
关键词[WOS]	PHOSPHOLIPASE-C ; STIMULATED NEUTROPHILS ; ACTIN DYNAMICS ; CELL BIOLOGY ; RHO-GTPASES ; ACTIVATION ; POLARITY ; DEPHOSPHORYLATION ; ROLES ; CDC42
收录类别	SCI
语种	英语
WOS记录号	WOS:000298215200010
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/816]
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	Tang, WW,Zhang, Y,Xu, WW,et al. A PLC beta/PI3K gamma-GSK3 Signaling Pathway Regulates Cofilin Phosphatase Slingshot2 and Neutrophil Polarization and Chemotaxis[J]. DEVELOPMENTAL CELL,2011,21(6):1038-1050.
APA	Tang, WW.,Zhang, Y.,Xu, WW.,Harden, TK.,Sondek, J.,...&Wu, DQ.(2011).A PLC beta/PI3K gamma-GSK3 Signaling Pathway Regulates Cofilin Phosphatase Slingshot2 and Neutrophil Polarization and Chemotaxis.DEVELOPMENTAL CELL,21(6),1038-1050.
MLA	Tang, WW,et al."A PLC beta/PI3K gamma-GSK3 Signaling Pathway Regulates Cofilin Phosphatase Slingshot2 and Neutrophil Polarization and Chemotaxis".DEVELOPMENTAL CELL 21.6(2011):1038-1050.