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Sarbassov, D.S., Guertin, D.A., Ali, S.M., Sabatini, D.M. (2005). Phosphorylation and regulation of Akt/PKB by the Rictor-mTOR complex.  Science 307(5712): 1098--1101.
FlyBase ID
FBrf0188463
Publication Type
Research paper
Abstract

Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser473 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 Ser473 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 Ser473 in vitro and facilitated Thr308 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.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Science
    Title
    Science
    Publication Year
    1895-
    ISBN/ISSN
    0036-8075
    Data From Reference
    Genes (7)
    Cell Lines (1)