Ligand-induced activation of ERK1/2 signaling by constitutively active G(s)-coupled 5-HT receptors

doi:10.1038/s41401-018-0204-6

	Ligand-induced activation of ERK1/2 signaling by constitutively active G(s)-coupled 5-HT receptors
	Liu, Ping 1,2; Yin, Yu-ling 1,2; Wang, Ting 1,2,3; Hou, Li 1; Wang, Xiao-xi 1; Wang, Man 1; Zhao, Guan-guan 1; Shi, Yi 1; Xu, H. Eric 1,2,3,4; Jiang, Yi 1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2019-09-01
卷号	40 期号:9 页码:1157-1167
关键词	5-HT4R 5-HT6R 5-HT7AR 5-HT ERK1/2 G(s) beta-arrestin Fyn Src
ISSN号	1671-4083
DOI	10.1038/s41401-018-0204-6
通讯作者	Xu, H. Eric(eric.xu@simm.ac.cn) ; Jiang, Yi(yijiang@simm.ac.cn)
英文摘要	5-HT4R, 5-HT6R, and 5-HT7AR are three constitutively active G(s)-coupled 5-HT receptors that have key roles in brain development, learning, memory, cognition, and other physiological processes in the central nervous system. In addition to G(s) signaling cascade mediated by these three 5-HT receptors, the ERK1/2 signaling which is dependent on cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activation downstream of G(s) signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three G(s)-coupled 5-HT receptors in AD293 cells. We found that the phosphorylation and activation of ERK1/2 are ligand-induced, in contrast to the constitutively active G(s) signaling. This indicates that G(s) signaling alone is not sufficient for ERK1/2 activation in these three 5-HT receptors. In addition to G(s), we found that beta-arrestin and Fyn are essential for the activation of ERK1/2. Together, these results put forth a novel mechanism for ERK1/2 activation involving the cooperative action of G(s), beta-arrestin, and Fyn.
资助项目	National Natural Science Foundation[31770796] ; National Science and Technology Major Project[2018ZX09711002-002-002] ; Ministry of Science and Technology of China[XDB08020303] ; K.C. Wong Education Foundation ; Youth Innovation Promotion Association of CAS ; Outstanding Young Scientist Foundation (CAS)
WOS关键词	G-PROTEIN ; BETA-ARRESTIN ; REGULATED KINASE ; SPLICE VARIANTS ; EXPRESSION ; PATHWAYS ; PARADIGMS ; MECHANISM ; MAPK ; SRC
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000484000100003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288832]
专题	中国科学院上海药物研究所
通讯作者	Xu, H. Eric; Jiang, Yi
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, VARI SIMM Ctr,Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA
推荐引用方式 GB/T 7714	Liu, Ping,Yin, Yu-ling,Wang, Ting,et al. Ligand-induced activation of ERK1/2 signaling by constitutively active G(s)-coupled 5-HT receptors[J]. ACTA PHARMACOLOGICA SINICA,2019,40(9):1157-1167.
APA	Liu, Ping.,Yin, Yu-ling.,Wang, Ting.,Hou, Li.,Wang, Xiao-xi.,...&Jiang, Yi.(2019).Ligand-induced activation of ERK1/2 signaling by constitutively active G(s)-coupled 5-HT receptors.ACTA PHARMACOLOGICA SINICA,40(9),1157-1167.
MLA	Liu, Ping,et al."Ligand-induced activation of ERK1/2 signaling by constitutively active G(s)-coupled 5-HT receptors".ACTA PHARMACOLOGICA SINICA 40.9(2019):1157-1167.