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The activation of the mitogen-activated protein(MAP)kinases extracellular signal-regulated kinase(ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors(GPCRs)via arrestins,as opposed to conventional GPCR signaling via G proteins.Several recent studies using HEK293 cells where all G proteins were genetically ablated or inactivated,or both non-visual arrestins were knocked out,demonstrated that ERK1/2 phosphorylation requires G protein activity,but does not necessarily require the presence of non-visual arrestins.This appears to contradict the prevailing paradigm.Here we discuss these results along with the recent data on gene edited cells and arrestinmediated signaling.We suggest that there is no real controversy.G proteins might be involved in the activation of the upstream-most MAP3Ks,although in vivo most MAP3K activation is independent of heterotrimeric G proteins,being initiated by receptor tyrosine kinases and/or integrins.As far as MAP kinases are concerned,the best-established role of arrestins is scaffolding of the three-tiered cascades(MAP3K-MAP2K-MAPK).Thus,it seems likely that arrestins,GPCRbound and free,facilitate the propagation of signals in these cascades,whereas signal initiation via MAP3K activation may be independent of arrestins.Different MAP3Ks are activated by various inputs,some of which are mediated by G proteins,particularly in cell culture,where we artificially prevent signaling by receptor tyrosine kinases and integrins,thereby favoring GPCR-induced signaling.Thus,there is no reason to change the paradigm:Arrestins and G proteins play distinct non-overlapping roles in cell signaling.
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篇名 Arrestin-mediated signaling:Is there a controversy?
来源期刊 世界生物化学杂志:英文版(电子版) 学科 生物学
关键词 G protein-coupled receptors ARRESTIN G protein SIGNALING Extracellular SIGNAL-REGULATED KINASE 1/2 c-Jun N-TERMINAL KINASE 3
年,卷(期) 2018,(3) 所属期刊栏目
研究方向 页码范围 25-35
页数 11页 分类号 Q
字数 语种
DOI
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G
protein-coupled
receptors
ARRESTIN
G
protein
SIGNALING
Extracellular
SIGNAL-REGULATED
KINASE
1/2
c-Jun
N-TERMINAL
KINASE
3
研究起点
研究来源
研究分支
研究去脉
引文网络交叉学科
相关学者/机构
期刊影响力
世界生物化学杂志:英文版(电子版)
季刊
1949-8454
北京市朝阳区东四环中路62号楼远洋国际中
出版文献量(篇)
391
总下载数(次)
0
总被引数(次)
0
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