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

Dos D. Sarbassov; David A. Guertin; Siraj M. Ali; David M. Sabatini

doi:10.1126/science.1106148

Abstract

Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr 308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser 473 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 Ser 473 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 473 in vitro and facilitated Thr 308 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.

Keywords

Protein kinase BmTORC2PI3K/AKT/mTOR pathwayPhosphorylationPTENRPTORCancer researchCell biologyKinaseBiologymTORC1Signal transduction

MeSH Terms

3-Phosphoinositide-Dependent Protein KinasesAdaptor ProteinsSignal TransducingAnimalsCarrier ProteinsCell LineCell LineTumorDrosophila ProteinsDrosophila melanogasterEnzyme ActivationHumansHydrophobic and Hydrophilic InteractionsImmunoprecipitationPhosphatidylinositol 3-KinasesPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRNA InterferenceRapamycin-Insensitive Companion of mTOR ProteinRegulatory-Associated Protein of mTORSerineTOR Serine-Threonine Kinases

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Publication Info

Year: 2005
Type: article
Volume: 307
Issue: 5712
Pages: 1098-1101
Citations: 6075
Access: Closed

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APA Style

                            
                                
                                    Dos D. Sarbassov, 
                                
                                    David A. Guertin, 
                                
                                    Siraj M. Ali
                                
                                et al.
                            
                            (2005). 
                            Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex. 
                            Science
                            , 307
                            (5712)
                            , 1098-1101.
                            https://doi.org/10.1126/science.1106148
                        

Identifiers

DOI: 10.1126/science.1106148
PMID: 15718470

Data Quality

Data completeness: 81%