Hu Q, Klippel A, Muslin A J, Fantl W J, Williams L T
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Science. 1995 Apr 7;268(5207):100-2. doi: 10.1126/science.7701328.
Phosphatidylinositol (Pl)-3 kinase is one of many enzymes stimulated by growth factors. A constitutively activated mutant, p110, that functions independently of growth factor stimulation was constructed to determine the specific responses regulated by Pl-3 kinase. The p110 protein exhibited high specific activity as a Pl-3 kinase and as a protein kinase. Expression of p110 in NIH 3T3 cells induced transcription from the fos promoter. Co-expression of dominant negative Ras blocked this response. When expressed in Xenopus laevis oocytes, p110 increased the amount of guanosine 5'-triphosphate-bound Ras, caused activation of the Ras effector Raf-1, and induced Ras-dependent oocyte maturation. These findings show that Pl-3 kinase can stimulate diverse Ras-dependent cellular processes, including oocyte maturation and fos transcription.
磷脂酰肌醇（PI）-3激酶是受生长因子刺激的众多酶之一。构建了一种组成型激活突变体p110，其功能独立于生长因子刺激，以确定PI-3激酶调节的特定反应。p110蛋白作为PI-3激酶和蛋白激酶表现出高比活性。p110在NIH 3T3细胞中的表达诱导了fos启动子的转录。显性负性Ras的共表达阻断了这种反应。当在非洲爪蟾卵母细胞中表达时，p110增加了结合鸟苷5'-三磷酸的Ras的量，导致Ras效应器Raf-1的激活，并诱导了Ras依赖性的卵母细胞成熟。这些发现表明，PI-3激酶可以刺激多种Ras依赖性细胞过程，包括卵母细胞成熟和fos转录。
