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

Science, 18 February 2005
Vol. 307, Issue 5712, p. 1098-1101
DOI: 10.1126/science.1106148

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

  1. Dos D. Sarbassov,
  2. David A. Guertin*,
  3. Siraj M. Ali*,
  4. David M. Sabatini
  1. 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.
  1. To whom correspondence should be addressed. E-mail: sabatini{at}wi.mit.edu
  • * These authors contributed equally to this work.

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.

    • Received for publication 7 October 2004.
    • Accepted for publication 23 December 2004.

    Citation:

    D. D. Sarbassov, D. A. Guertin, S. M. Ali, and D. M. Sabatini, Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex. Science 307, 1098-1101 (2005).

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