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Abl酪氨酸激酶在Rho家族小GTP酶的上下游调节钙黏蛋白依赖性黏附。

Abl tyrosine kinases modulate cadherin-dependent adhesion upstream and downstream of Rho family GTPases.

作者信息

Zandy Nicole L, Pendergast Ann Marie

机构信息

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Cell Cycle. 2008 Feb 15;7(4):444-8. doi: 10.4161/cc.7.4.5452. Epub 2007 Dec 12.

Abstract

Formation and dissolution of intercellular adhesions are processes of paramount importance during tissue morphogenesis and for pathological conditions such as tumor metastasis. Cadherin-mediated intercellular adhesion requires dynamic regulation of the actin cytoskeleton. The pathways that link cadherin signaling to cytoskeletal regulation remain poorly defined. We have recently uncovered a novel role for the Abl family of tyrosine kinases linking cadherin-mediated adhesion to actin dynamics via the regulation of Rho family GTPases. Abl kinases are activated by cadherin engagement, localize to cell-cell junctions and are required for the formation of adherens junctions. Notably, we showed that Abl kinases are required for Rac activation during formation of adherens junctions, and also regulate a Rho-ROCK-myosin signaling pathway that is required for the maintenance of intercellular adhesion. Here we show that Abl kinases regulate the formation and strengthening of adherens junctions downstream of active Rac, and that Abl tyrosine kinases are components of a positive feed-back loop that employs the Crk/CrkL adaptor proteins to promote the formation and maturation of adherens junctions.

摘要

细胞间黏附的形成与解离是组织形态发生过程中以及诸如肿瘤转移等病理状况下极为重要的过程。钙黏蛋白介导的细胞间黏附需要对肌动蛋白细胞骨架进行动态调控。将钙黏蛋白信号传导与细胞骨架调控联系起来的途径仍未完全明确。我们最近发现了酪氨酸激酶Abl家族的一个新作用,即通过调节Rho家族GTP酶将钙黏蛋白介导的黏附与肌动蛋白动力学联系起来。Abl激酶通过钙黏蛋白的结合而被激活,定位于细胞间连接,并且是黏着连接形成所必需的。值得注意的是,我们表明Abl激酶在黏着连接形成过程中是Rac激活所必需的,并且还调节维持细胞间黏附所需的Rho-ROCK-肌球蛋白信号通路。在这里我们表明,Abl激酶在活性Rac下游调节黏着连接的形成和强化,并且Abl酪氨酸激酶是一个正反馈环的组成部分,该正反馈环利用Crk/CrkL衔接蛋白来促进黏着连接的形成和成熟。

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