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G蛋白偶联受体刺激与细胞迁移的调控。

G protein-coupled receptors stimulation and the control of cell migration.

作者信息

Cotton Mathieu, Claing Audrey

机构信息

Department of Pharmacology, University of Montreal, Montreal, QC, Canada.

出版信息

Cell Signal. 2009 Jul;21(7):1045-53. doi: 10.1016/j.cellsig.2009.02.008. Epub 2009 Feb 25.

Abstract

Cell migration is a fundamental biological process involved in normal physiology. Altered motile phenotypes are however often associated with the development and progression of diseases such as cancer and atherosclerosis. Remodeling of the actin cytoskeleton is required for cell shape changes and is controlled by a broad variety of cellular proteins. Interestingly, several extracellular stimuli can promote actin reorganization and result in enhanced cell migration. Namely, G protein-coupled receptors (GPCRs), which are activated by factors ranging from small amines, to hormones, and chemokines, initiate signalling cascades resulting in cell shape changes, formation of a migrating front (leading edge) and altered adhesion. GPCRs are heptahelical membrane proteins, which classically transmit signal via the activation of heterotrimeric G proteins. Sustained stimulation leads to the activation of G protein-coupled receptor kinases (GRKs) and the recruitment of arrestin proteins, which engage alternative signalling pathways. In this review, we will discuss the role of GPCR mediated signal transduction and review their importance in the regulation of actin remodeling leading to cell migration.

摘要

细胞迁移是正常生理过程中涉及的一个基本生物学过程。然而,改变的运动表型通常与癌症和动脉粥样硬化等疾病的发生和发展相关。肌动蛋白细胞骨架的重塑是细胞形态变化所必需的,并受多种细胞蛋白的控制。有趣的是,几种细胞外刺激可促进肌动蛋白重组并导致细胞迁移增强。具体而言,G蛋白偶联受体(GPCR)可被从小胺类到激素和趋化因子等多种因子激活,启动信号级联反应,导致细胞形态变化、形成迁移前沿(前缘)和改变黏附。GPCR是七螺旋膜蛋白,经典地通过激活异源三聚体G蛋白来传递信号。持续刺激会导致G蛋白偶联受体激酶(GRK)的激活和抑制蛋白的募集,从而启动替代信号通路。在本综述中,我们将讨论GPCR介导的信号转导的作用,并综述它们在调节导致细胞迁移的肌动蛋白重塑中的重要性。

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