Phosphatidylinositol-3-OH kinase as a direct target of Ras.
Ras (p21ras) interacts directly with the catalytic subunit of phosphatidylinositol-3-OH kinase in a GTP-dependent manner through the Ras effector site. In vivo, dominant negative Ras mutant N17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in PC12 cells, and transfection of Ras, but not Raf, into COS cells results in a large elevation in the level of these lipids. Therefore Ras can probably regulate phosphatidylinositol-3-OH kinase, providing a point of divergence in signalling pathways downstream of Ras.
Rodriguez-Viciana
P
P
Imperial Cancer Research Fund, London, UK.
Warne
P H
PH
Dhand
R
R
Vanhaesebroeck
B
B
Gout
I
I
Fry
M J
MJ
Waterfield
M D
MD
Downward
J
J
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000502:physiology; D011905:Genes, ras; D006160:Guanosine Triphosphate / Q000378:metabolism; D009154:Mutation; D009414:Nerve Growth Factors / Q000502:physiology; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D051381:Rats
D009414:Nerve Growth Factors; D018129:Phosphatidylinositol Phosphates; D004815:Epidermal Growth Factor; D006160:Guanosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D016283:Proto-Oncogene Proteins p21(ras)