A FAK-Cas-Rac-lamellipodin signaling module transduces extracellular matrix stiffness into mechanosensitive cell cycling.
A FAK-Cas-Rac-lamellipodin signaling module transduces extracellular matrix stiffness into mechanosensitive cell cycling.
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DOI：
10.1126/scisignal.2004838
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发表时间：
2014-06-17
影响因子：
7.3
通讯作者：
Assoian RK
中科院分区：
文献类型：
--
作者：
Bae YH;Mui KL;Hsu BY;Liu SL;Cretu A;Razinia Z;Xu T;Puré E;Assoian RK
组织和细胞外基质 (ECM) 硬度转化为细胞内硬度、信号传导和细胞行为的变化。整合素和一些相关的粘着斑蛋白与 ECM 硬度的传感有关。我们研究了初始传感事件如何转化为细胞内硬度和生物可解释的信号。我们发现，由粘着斑激酶（FAK）、接头蛋白p130Cas（Cas）和鸟苷三磷酸酶Rac组成的通路选择性地将ECM硬度转化为稳定的细胞内硬度，增加细胞周期蛋白cyclin D1的丰度，并促进进入S期。 Rac 依赖性细胞内硬化涉及其结合伙伴板脂蛋白，板脂蛋白是一种在细胞迁移过程中将 Rac 信号传递到细胞骨架的蛋白质。我们的研究结果表明，FAK-Cas-Rac-lamellipodin 信号模块的机械转导可将 ECM 刚度编码的外部信息转化为稳定的细胞内刚度和机械敏感细胞循环。因此，板脂蛋白不仅在控制细胞迁移方面很重要，而且在响应机械信号而调节细胞周期方面也很重要。
Tissue and extracellular matrix (ECM) stiffness is transduced into intracellular stiffness, signaling, and changes in cellular behavior. Integrins and several of their associated focal adhesion proteins have been implicated in sensing ECM stiffness. We investigated how an initial sensing event is translated into intracellular stiffness and a biologically interpretable signal. We found that a pathway consisting of focal adhesion kinase (FAK), the adaptor protein p130Cas (Cas), and the guanosine triphosphatase Rac selectively transduced ECM stiffness into stable intracellular stiffness, increased abundance of the cell cycle protein cyclin D1, and promoted S phase entry. Rac-dependent intracellular stiffening involved its binding partner lamellipodin, a protein that transmits Rac signals to the cytoskeleton during cell migration. Our findings establish that mechanotransduction by a FAK-Cas-Rac-lamellipodin signaling module converts the external information encoded by ECM stiffness into stable intracellular stiffness and mechanosensitive cell cycling. Thus, lamellipodin is not only important in controlling cellular migration, but also for regulating the cell cycle in response to mechanical signals.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Fonseca, PM;Shin, NY;Hanks, SK
通讯作者：
Hanks, SK
影响因子：
56.9
作者：
Baarlink, Christian;Wang, Haicui;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
4
作者：
Ballestrem, C;Erez, N;Geiger, B
通讯作者：
Geiger, B
影响因子：
3.4
作者：
Fabry, Ben;Klemm, Anna H.;Goldmann, Wolfgang H.
通讯作者：
Goldmann, Wolfgang H.