Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex
Copyright policy )Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex
Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr 308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser 473 within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that in Drosophila and human cells the target of rapamycin (TOR) kinase and its associated protein rictor are necessary for Ser 473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on Ser 473 in vitro and facilitated Thr 308 phosphorylation by PDK1. Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation.
- Massachusetts Institute of Technology United States
Proteins, Protein Serine-Threonine Kinases, Cell Line, 3-Phosphoinositide-Dependent Protein Kinases, Enzyme Activation, Phosphatidylinositol 3-Kinases, Drosophila melanogaster, Cell Line, Tumor, Proto-Oncogene Proteins, Animals, Drosophila Proteins, Humans, Immunoprecipitation, RNA Interference, Phosphorylation, Carrier Proteins, Hydrophobic and Hydrophilic Interactions, Protein Kinases, Proto-Oncogene Proteins c-akt, Adaptor Proteins, Signal Transducing
Proteins, Protein Serine-Threonine Kinases, Cell Line, 3-Phosphoinositide-Dependent Protein Kinases, Enzyme Activation, Phosphatidylinositol 3-Kinases, Drosophila melanogaster, Cell Line, Tumor, Proto-Oncogene Proteins, Animals, Drosophila Proteins, Humans, Immunoprecipitation, RNA Interference, Phosphorylation, Carrier Proteins, Hydrophobic and Hydrophilic Interactions, Protein Kinases, Proto-Oncogene Proteins c-akt, Adaptor Proteins, Signal Transducing
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