Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling.

Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling.
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DOI:
10.1016/j.tibs.2011.06.003
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发表时间:
2011-09
影响因子:
13.8
通讯作者:
Lefkowitz, Robert J.
Lefkowitz, Robert J.
中科院分区:
生物学1区
文献类型:
--
作者:
Shukla, Arun K.;Xiao, Kunhong;Lefkowitz, Robert J.

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β-阻滞蛋白最初被发现可使7种被激活的跨膜受体(7TMRs,也称为G蛋白偶联受体[gpcr])脱敏,现在已被广泛认为是受体内吞作用、泛素化和G蛋白非依赖性信号传导的介质。最近对β-阻滞蛋白相互作用和β-阻滞蛋白依赖磷酸化事件的全球分析揭示了β-阻滞蛋白在一系列细胞信号传导事件中的几个先前未预料到的作用。这些发现有力地表明β-抑制因子的功能作用比目前所了解的要广泛得多。生物物理研究旨在了解7tmr和β-阻滞蛋白的多种活性构象,已经开始揭示β-阻滞蛋白在细胞信号传导中的多种功能能力的机制基础。
β-arrestins, originally discovered to desensitize activated seven transmembrane receptors (7TMRs; also known as G protein-coupled receptors [GPCRs]), are now well established mediators of receptor endocytosis, ubiquitylation and G protein-independent signaling. Recent global analyses of β-arrestin interactions and β-arrestin-dependent phosphorylation events have uncovered several previously unanticipated roles of β-arrestins in a range of cellular signaling events. These findings strongly suggest that the functional roles of β-arrestins are much broader than currently understood. Biophysical studies aimed at understanding multiple active conformations of the 7TMRs and the β-arrestins have begun to unravel the mechanistic basis for the diverse functional capabilities of β-arrestins in cellular signaling.
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