Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27(KIP1)
Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27(KIP1)
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DOI：
10.1128/mcb.17.7.3850
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发表时间：
1997-07-01
影响因子：
5.3
通讯作者：
Cooper, GM
中科院分区：
文献类型：
--
作者：
Aktas, H;Cai, H;Cooper, GM
通过配体结合激活生长因子受体启动导致细胞生长和分裂的级联事件。细胞周期的进程是由细胞周期蛋白依赖性蛋白激酶（Cdks）控制的，但将生长因子信号传导与细胞周期机制联系起来的机制尚未建立。我们在此报道Ras蛋白在整合促有丝分裂信号与细胞周期进程中起关键作用。Ras是细胞周期进程和Cdk 2和Cdk 4激活所必需的，直到类似于G（I）/S转换前2小时，对应于限制点。Cdk-细胞周期蛋白复合物的分析表明，Res信号传导是诱导细胞周期蛋白D1和下调Cdk抑制剂p27（KIP 1）所必需的。细胞周期蛋白D1的组成性表达绕过了细胞增殖中对Bas信号的需要，表明细胞周期蛋白D1的调节是Res信号级联的关键靶点。
Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the fell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established, We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G(I). Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until similar to 2 h before the G(I)/S transition, corresponding to the restriction point, Analysis of Cdk-cyclin complexes indicates that Res signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27(KIP1). Constitutive expression of cyclin D1 circumvents the requirement for Bas signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Res signaling cascade.