Editors' ChoiceCancer

Getting In on the Akt

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Science's STKE  22 Feb 2005:
Vol. 2005, Issue 272, pp. tw74
DOI: 10.1126/stke.2722005tw74

Akt [also known as protein kinase B (PKB)] is deregulated in many human cancers. Sarbassov et al. have identified an enzyme in Drosophila and human cells that initiates its activation. Upon association with the cytoplasmic protein rictor, the cytoplasmic kinase mammalian target of rapamycin (mTOR) phosphorylates a critical hydrophobic motif in Akt/PKB. This modification is required for full activation of Akt and its subsequent regulation of cell survival. In contrast, association of mTOR with another cytoplasmic protein, raptor, does not target Akt and is sensitive to the drug rapamycin. Reduced expression of mTOR or rictor blocked Akt activity, which suggests that the complex may serve as an effective target in cancer cells for drug development.

D. D. Sarbassov, D. A. Guertin, S. M. Ali, D. M. Sabatini, Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101 (2005). [Abstract] [Full Text]

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