An activity-based probe reveals dynamic protein-protein interactions mediating IGF-1R transactivation by the GABA(B) receptor

doi:10.1042/BJ20120188

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	An activity-based probe reveals dynamic protein-protein interactions mediating IGF-1R transactivation by the GABA(B) receptor
	Lin, Xin 1; Li, Xin 2; Jiang, Ming 1; Chen, Linhai2 ; Xu, Chanjuan 1; Zhang, Wenhua 1; Zhao, Han 1; Sun, Bing 1; Xu, Xiaoli 1; Nan, Fajun2
刊名	BIOCHEMICAL JOURNAL
	2012-05-01
卷号	443 页码:627-634
关键词	activity-based probe gamma-aminobutyric acid B receptor (GABA(B) receptor) dynamic protein-protein interaction insulin-like growth factor type I receptor (IGF-1R) transactivation
ISSN号	0264-6021
DOI	10.1042/BJ20120188
文献子类	Article
英文摘要	Many GPCRs (G-protein-coupled receptors) can activate RTKs (receptor tyrosine kinases) in the absence of RTK ligands, a phenomenon called transactivation. However, the underlying molecular mechanisms remain undefined. In the present study we investigate the molecular basis of GABA(B) (gamma-aminobutyric acid B) receptor-mediated transactivation of IGF-1R (insulin-like growth factor type I receptor) in primary neurons. We take a chemical biology approach by developing an activity-based probe targeting the GABA(B) receptor. This probe enables us first to lock the GABA(B) receptor in an inactive state and then activate it with a positive allosteric modulator, thereby permitting monitoring of the dynamic of the protein complex associated with IGF-1R transactivation. We find that activation of the GABA(B) receptor induces a dynamic assembly and disassembly of a protein complex, including both receptors and their downstream effectors. FAK (focal adhesion kinase), a non-RTK, plays a key role in co-ordinating this dynamic process. Importantly, this dynamic of the GABA(B) receptor-associated complex is critical for transactivation and transactivation-dependent neuronal survival. The present study has identified an important mechanism underlying GPCR transactivation of RTKs, which was enabled by a new chemical biology tool generally applicable for dissecting GPCR signalling.
资助项目	Ministry of Science and Technology[2007CB914200] ; Ministry of Science and Technology[2010DFA32140] ; National Natural Science Foundation of China (NSFC)[31130028] ; National Natural Science Foundation of China (NSFC)[30973514] ; Ministry of Education[B08029] ; National Basic Research Program of China[2007CB914200] ; National Natural Science Foundation of China[30725049] ; National Natural Science Foundation of China[90813037]
WOS关键词	GROWTH-FACTOR RECEPTOR ; SIGNAL-REGULATED KINASE ; G-BETA-GAMMA ; COUPLED RECEPTORS ; LIVING CELLS ; ACTIVATION ; SURVIVAL ; LIGANDS ; SUBUNIT ; NEURONS
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	PORTLAND PRESS LTD
WOS记录号	WOS:000303944200004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278092]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Nan, Fajun
作者单位	1.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Minist Educ, Key Lab Mol Biophys,Sinofrance Lab Drug Screening, Wuhan 430074, Hubei, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res,Natl Ctr Drug Screening, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Lin, Xin,Li, Xin,Jiang, Ming,et al. An activity-based probe reveals dynamic protein-protein interactions mediating IGF-1R transactivation by the GABA(B) receptor[J]. BIOCHEMICAL JOURNAL,2012,443:627-634.
APA	Lin, Xin.,Li, Xin.,Jiang, Ming.,Chen, Linhai.,Xu, Chanjuan.,...&Liu, Jianfeng.(2012).An activity-based probe reveals dynamic protein-protein interactions mediating IGF-1R transactivation by the GABA(B) receptor.BIOCHEMICAL JOURNAL,443,627-634.
MLA	Lin, Xin,et al."An activity-based probe reveals dynamic protein-protein interactions mediating IGF-1R transactivation by the GABA(B) receptor".BIOCHEMICAL JOURNAL 443(2012):627-634.