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

  title={Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex},
  author={Dos D. Sarbassov and David A Guertin and Siraj M. Ali and David M. Sabatini},
  pages={1098 - 1101}
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… 

Rictor Phosphorylation on the Thr-1135 Site Does Not Require Mammalian Target of Rapamycin Complex 2

It is found that this rictor phosphorylation takes place in the m TORC2-deficient cells, suggesting that this modification might play a role in the regulation of not only mTORC2 but also the mTORc2-independent function of rictsor.

Receptor-Specific Mechanisms Regulate Phosphorylation of AKT at Ser473: Role of RICTOR in β1 Integrin-Mediated Cell Survival

It is demonstrated that different receptors utilise different enzyme complexes to phosphorylate AKT at Ser473, and that AKT Ser473 phosphorylation significantly contributes to β1 integrin-mediated anchorage-dependent survival of cells.

Rictor is a novel target of p70 S6 kinase-1

It is demonstrated here that Rictor is a direct target of the ribosomal protein S6 kinase-1 (S6K1), which reveals an unexpected signaling input into mTORC2, which is regulated by amino acids, growth factors and rapamycin.

Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth.

Loss of TORC2 activity strongly inhibited hyperplasia caused by elevated pathway activity, as in mutants of the tumor suppressor PTEN, and acts as a rheostat to broaden the range of AKT signaling at the high end of its range.

IκB kinase ε and TANK-binding kinase 1 activate AKT by direct phosphorylation

It is shown that the atypical IκB kinase ε and TANK-binding kinase 1 (IKKε/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling, which results in a robust AKT activation in vitro.

PRR5L degradation promotes MTORC2-mediated PKCδ phosphorylation and cell migration downstream of Gα12

It is shown that lysophosphatidic acid (LPA) induces two phases of PKC-δ hydrophobic motif phosphorylation, which is critically important for fibroblast migration and pulmonary fibrosis development.

Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition

A-443654 induces Akt Ser-473 phosphorylation in all human cancer cell lines tested, including PTEN- and TSC2-deficient lines, and provides a novel mode of Akt regulation that is distinct from the previously described rapamycin-induced IRS-1 stabilization mechanism.

Scaffolding function of PAK in the PDK1–Akt pathway

It is shown that Rac1 stimulates a second, kinase-independent function of PAK1, which serves as a scaffold to facilitate Akt stimulation by PDK1 and to aid recruitment of Akt to the membrane.

Obligate Role of Anti-Apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells

Myeloid leukemia–1 (MCL-1) is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitor populations, including HSCs.


Recently, many cellular oncogenes were identified in human cancerous cells by the DNA transfection method, some of which were found to contain sequences related with already known viral oncogenees.


St. Jude Children's Research Hospital.

  • C. Pratt
  • Medicine
    Pediatric hematology and oncology
  • 1997
Award Title: Therapeutics for regeneration of fully functional auditory outer hair cells and its applications in music therapy and regenerative medicine.

References and Notes

our experimentation could eventually be used to discredit our findings, should they happen not to agree with the original observations. It seems important that all experiments in the rapidly

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