哺乳动物细胞的转化由构成性活性MAP激酶激酶激酶转化
S J Mansour1, W T Matten, A S Hermann
1Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.
概括
构成性活跃的基激活蛋白激酶激酶 (MAPKK) 突变促进了细胞转化. 这些发现表明,MAPKK激活对于瘤发生是足够的,影响了癌症研究.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 信号传导途径的信号传导途径.
背景情况:
- 线素激活蛋白 (MAP) 激酶激酶 (MAPKK) 在调节细胞对生长和分化因子反应的信号传导途径中至关重要.
- 假设ras, src, raf和mos等瘤基因通过维持MAPKK激活引起细胞转化.
研究的目的:
- 调查MAPKK的持续激活是否足以诱导细胞转化.
- 测试瘤转化涉及长时间激活MAPKK和下游信号组件的假设.
主要方法:
- 改造的构成性活跃的MAPKK突变体具有显著升高的基底活性 (高达野生类型的400倍).
- 在哺乳动物细胞中表达了这些突变.
- 在裸体小鼠中评估了AP-1-调节的转录,软菌殖民地形成和瘤性.
主要成果:
- 构成性活跃的MAPKK突变体的表达导致AP-1-调节转录的激活.
- 表达这些突变的细胞表现出转变的焦点形成.
- 这些细胞在裸体小鼠中表现出高效增长的软和高瘤性.
结论:
- 构成MAPKK的激活足以促进细胞转化.
- 这项研究提供了直接证据,将MAPKK过活化与瘤发生联系起来.
- 这些发现对理解癌症发展和确定治疗点有重要意义.
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