Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase

Science. 1995 Apr 7;268(5207):100-2. doi: 10.1126/science.7701328.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Genes, fos / genetics
  • Mice
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / biosynthesis
  • Phosphotransferases (Alcohol Group Acceptor) / physiology*
  • Promoter Regions, Genetic / physiology
  • Recombinant Fusion Proteins / biosynthesis
  • Signal Transduction / physiology*
  • Transcription, Genetic / physiology
  • Xenopus laevis
  • ras Proteins / physiology*

Substances

  • Recombinant Fusion Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • ras Proteins