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

by: Dos D Sarbassov, David A Guertin, Siraj M Ali, David M Sabatini

Science, Vol. 307, No. 5712. (18 February 2005), pp. 1098-1101.

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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.

@article{citeulike:100040, 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.}, author = {Sarbassov, Dos D. and Guertin, David A. and Ali, Siraj M. and Sabatini, David M. }, citeulike-article-id = {100040}, doi = {10.1126/science.1106148}, journal = {Science}, month = {February}, number = {5712}, pages = {1098--1101}, posted-at = {2008-02-10 03:29:00}, priority = {2}, title = {Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex}, url = {http://dx.doi.org/10.1126/science.1106148}, volume = {307}, year = {2005} }

RIS record

TY - JOUR ID - citeulike:100040 L3 - citeulike-article-id:100040 TI - Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex JF - Science VL - 307 IS - 5712 SP - 1098 EP - 1101 N2 - 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. AU - Sarbassov, Dos AU - Guertin, David AU - Ali, Siraj AU - Sabatini, David PY - 2005/02/18/ UR - http://dx.doi.org/10.1126/science.1106148 ER -

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