Meloche S, Pouysségur J
Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montreal, Quebec, Canada.
Oncogene. 2007 May 14;26(22):3227-39. doi: 10.1038/sj.onc.1210414.
The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway plays a central role in cell proliferation control. In normal cells, sustained activation of ERK1/ERK2 is necessary for G1- to S-phase progression and is associated with induction of positive regulators of the cell cycle and inactivation of antiproliferative genes. In cells expressing activated Ras or Raf mutants, hyperactivation of the ERK1/2 pathway elicits cell cycle arrest by inducing the accumulation of cyclin-dependent kinase inhibitors. In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies.
依赖Ras的细胞外信号调节激酶（ERK）1/2丝裂原活化蛋白（MAP）激酶途径在细胞增殖控制中起核心作用。在正常细胞中，ERK1/ERK2的持续激活对于G1期到S期的进展是必需的，并且与细胞周期正调节因子的诱导和抗增殖基因的失活相关。在表达活化Ras或Raf突变体的细胞中，ERK1/2途径的过度激活通过诱导细胞周期蛋白依赖性激酶抑制剂的积累而引发细胞周期停滞。在本综述中，我们讨论了活化的ERK1/2调节哺乳动物体细胞生长和细胞周期进程的机制。我们还强调了基因敲除研究获得的结果。
