RAS-DEPENDENT INDUCTION OF CELLULAR-RESPONSES BY CONSTITUTIVELY ACTIVE PHOSPHATIDYLINOSITOL-3 KINASE

Phosphatidylinositol (PI)-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 PI-3 kinase. The p110* protein exhibited high specific activity as a PI-3 kinase and as a protein kinase. Expression of p110* in NIH 3T3 cells induced transcription from the fos promoter. Coexpression 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 PI-3 kinase can Stimulate diverse Ras-dependent cellular processes, including oocyte maturation and fos transcription.