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PINCH-ILK-帕文复合物:组装、功能与调控

The PINCH-ILK-parvin complexes: assembly, functions and regulation.

作者信息

Wu Chuanyue

机构信息

Department of Pathology, University of Pittsburgh, 707B Scaife Hall, 3550 Terrace Street, PA 15261, USA.

出版信息

Biochim Biophys Acta. 2004 Jul 5;1692(2-3):55-62. doi: 10.1016/j.bbamcr.2004.01.006.

Abstract

Cell-extracellular matrix (ECM) adhesion is mediated by transmembrane cell adhesion receptors (e.g., integrins) and receptor proximal cytoplasmic proteins. Over the past several years, studies using biochemical, structural, cell biological and genetic approaches have provided important evidence suggesting crucial roles of integrin-linked kinase (ILK), PINCH and CH-ILKBP/actopaxin/affixin/parvin (abbreviated as parvin herein) in ECM control of cell behavior. One general theme emerging from these studies is that the formation of ternary protein complexes consisting of ILK, PINCH and parvin is pivotal to the functions of PINCH, ILK and parvin proteins. In addition, recent studies have begun to uncover the molecular mechanisms underlying the assembly, functions and regulation of the PINCH-ILK-parvin (PIP) complexes. The PIP complexes provide crucial physical linkages between integrins and the actin cytoskeleton and transduce diverse signals from ECM to intracellular effectors. Among the challenges of future studies are to define the functions of different PIP complexes in various cellular processes, identify additional partners of the PIP complexes that regulate and/or mediate the functions of the PIP complexes, and determine the roles of the PIP complexes in the pathogenesis of human diseases involving abnormal cell-ECM adhesion and signaling.

摘要

细胞与细胞外基质(ECM)的黏附由跨膜细胞黏附受体(如整合素)和受体近端细胞质蛋白介导。在过去几年中,利用生化、结构、细胞生物学和遗传学方法进行的研究提供了重要证据,表明整合素连接激酶(ILK)、PINCH和CH-ILKBP/桩蛋白/亲和蛋白/纽蛋白(本文简称为纽蛋白)在ECM对细胞行为的调控中发挥关键作用。这些研究中出现的一个普遍主题是,由ILK、PINCH和纽蛋白组成的三元蛋白复合物的形成对于PINCH、ILK和纽蛋白的功能至关重要。此外,最近的研究开始揭示PINCH-ILK-纽蛋白(PIP)复合物组装、功能和调控的分子机制。PIP复合物在整合素和肌动蛋白细胞骨架之间提供关键的物理连接,并将多种信号从ECM传递至细胞内效应器。未来研究面临的挑战包括确定不同PIP复合物在各种细胞过程中的功能,识别调控和/或介导PIP复合物功能的PIP复合物的其他伙伴,以及确定PIP复合物在涉及异常细胞-ECM黏附和信号传导的人类疾病发病机制中的作用。

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