Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase.
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.
Hu
Q
Q
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Klippel
A
A
Muslin
A J
AJ
Fantl
W J
WJ
Williams
L T
LT
D016475:3T3 Cells; D000818:Animals; D016762:Genes, fos / Q000235:genetics; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D014982:Xenopus laevis; D018631:ras Proteins / Q000502:physiology*
D011993:Recombinant Fusion Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D018631:ras Proteins