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黏着斑激酶(FAK)控制着机械激活的 Yes 相关蛋白(YAP),后者是趋硬性所必需的转录调控因子。

FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis.

机构信息

Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, United Kingdom; and.

Regenerative Medicine and Fibrosis Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, United Kingdom.

出版信息

FASEB J. 2018 Feb;32(2):1099-1107. doi: 10.1096/fj.201700721R. Epub 2018 Jan 3.

Abstract

Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes in cells such as growth, survival, and migration. FAK is one of the first molecules recruited to focal adhesions in response to external mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling, and relays these stimuli to other mechanotransducers within the cytoplasm. Yes-associated protein (YAP) has been identified recently as one of these core mechanotransducers. YAP translocates to the nucleus following changes in cell mechanics to promote the expression of genes implicated in motility, apoptosis, proliferation, and organ growth. Here, we show that FAK controls the nuclear translocation and activation of YAP in response to mechanical activation and submit that the YAP-dependent process of durotaxis requires a cell with an asymmetric distribution of active and inactive FAK molecules.-Lachowski, D., Cortes, E., Robinson, B., Rice, A., Rombouts, K., Del Río Hernández, A. E. FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis.

摘要

黏着斑激酶(FAK)是黏着斑中的关键分子,调节细胞中的基本过程,如生长、存活和迁移。FAK 是对外部机械刺激做出反应而首先招募到黏着斑中的分子之一,因此是细胞机械信号转导的关键介质,并将这些刺激传递到细胞质内的其他机械转导器。Yes 相关蛋白(YAP)最近被确定为这些核心机械转导器之一。细胞力学发生变化后,YAP 易位到细胞核,促进与运动、凋亡、增殖和器官生长相关的基因表达。在这里,我们表明 FAK 控制 YAP 的核易位和激活,以响应机械激活,并提出依赖于 YAP 的趋硬性过程需要具有活性和非活性 FAK 分子不均匀分布的细胞。-Lachowski,D.,Cortes,E.,Robinson,B.,Rice,A.,Rombouts,K.,del Río Hernández,A. E. FAK 控制着 YAP 的机械激活,YAP 是趋硬性所必需的转录调节剂。

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