Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex

DOI Web Site 被引用文献176件
  • Dos D. Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA. Broad Institute, 320 Charles Street, Cambridge, MA 02141, USA.
  • David A. Guertin
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA. Broad Institute, 320 Charles Street, Cambridge, MA 02141, USA.
  • Siraj M. Ali
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA. Broad Institute, 320 Charles Street, Cambridge, MA 02141, USA.
  • David M. Sabatini
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA. Broad Institute, 320 Charles Street, Cambridge, MA 02141, USA.

書誌事項

公開日
2005-02-18
DOI
  • 10.1126/science.1106148
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:p> Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr <jats:sup>308</jats:sup> in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser <jats:sup>473</jats:sup> within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that in <jats:italic>Drosophila</jats:italic> and human cells the target of rapamycin (TOR) kinase and its associated protein rictor are necessary for Ser <jats:sup>473</jats:sup> 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 <jats:sup>473</jats:sup> in vitro and facilitated Thr <jats:sup>308</jats:sup> 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. </jats:p>

収録刊行物

  • Science

    Science 307 (5712), 1098-1101, 2005-02-18

    American Association for the Advancement of Science (AAAS)

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