Proceedings of the National Academy of Sciences · 1998 · 300 citations · 43 references
Life SciencesMolecular BiologyOncologyCell SignalingMolecular OncologySignal TransductionOncogene ActivationOncogene MutationsOncogenic Signaling PathwaysPhosphoinositide SignalingProtein Kinase CascadesProto-oncogene ActivationOncogenic TransformationPhosphatidylinositol 3-Kinase Akt SignalingPhosphatidylinositol 3-Kinase-akt SignalingPhosphoinositide 3-Kinase SignalingPhosphoinositide 3-Kinase-akt ActivationPhosphoinositide 3-Kinase-akt SignalingPhosphoinositide KinasesPi3k Signaling
The serine-threonine kinase Akt is a downstream target of phosphoinositide 3-kinase (PI 3-kinase); it is activated by the phosphoinositide 3-phosphate-dependent kinases PDK1 and PDK2. Certain mutated forms of Akt induce oncogenic transformation in chicken embryo fibroblast cultures and hemangiosarcomas in young chickens. This ability to transform cells depends on localization of Akt at the plasma membrane and on the kinase activity of Akt. A transdominant negative form of Akt interferes with oncogenic transformation induced by the p3k oncogene, which codes for an activated form of PI 3-kinase. Akt is therefore an essential mediator of p3k-induced oncogenicity.
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