具有高或低GTPase活性的Ras p21蛋白可以有效地转化NIH/3T3细胞
Cell
|February 28, 1986
概括
Ras p21突变可以在没有减少GTPase活性的情况下获得转化性质. 这项研究表明,高效的转化可以通过替代机制发生,挑战了关于ras瘤基因激活的先前假设.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- Ras p21蛋白质是细胞信号的关键调节者.
- 拉斯p21突变体的GTPase活性降低通常与瘤转化有关.
- 驱动ras介导转换的精确机制需要进一步阐明.
研究的目的:
- 为了研究体外GTPase活性与ras p21突变体的转化性质之间的关系.
- 为了确定减少的GTPase活性是否是ras p21驱动的细胞转换的普遍要求.
主要方法:
- 在体外对正常和突变的H-ras p21蛋白进行了GTPase活性测定.
- 细菌表达的正常H-ras p21和各种p21突变物被微注入NIH/3T3细胞中.
- 微注射后评估了细胞形态变化和DNA合成.
- 用真核体载体表达的突变物的转化活性与正常的H-ras.相比较.
主要成果:
- 突变H-ras p21-[Lys12-Ala59]和H-ras p21-[Arg12-Thr59]的体外GTPase活性与正常的H-ras p21-[Gly12-Ala59]和H-ras p21-[Gly12-Thr59]相比显著降低.
- 低度的p21突变诱导NIH/3T3细胞形态变化和DNA合成,与正常的p21不同.
- 突变ras p21蛋白质的转化活性至少是正常H-ras基因的100倍.
结论:
- 拉斯p21蛋白质的高效转化特性可以独立于体外GTPase活性降低而被激活.
- 这些发现表明ras瘤基因激活和转换的替代途径.
- 这项研究挑战了减少GTPase功能对于ras驱动的瘤发生是必不可少的范式.
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