PatentDOI
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
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TLDR
In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.Abstract:
In certain aspects, the invention relates to methods for identifying compounds which modulate Akt activity mediated by the rictor-mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activity.read more
Citations
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Journal ArticleDOI
mTOR signaling in growth control and disease.
TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
Journal ArticleDOI
TOR signaling in growth and metabolism.
TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.
Journal ArticleDOI
mTOR Signaling in Growth, Metabolism, and Disease.
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR signaling network contributes to human disease is highlighted.
Journal ArticleDOI
mTOR: from growth signal integration to cancer, diabetes and ageing
TL;DR: Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.
Journal ArticleDOI
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
TL;DR: In light of the recent advances in understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, the exciting therapeutic opportunities for targeting this pathway to treat these diseases are discussed.
References
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Journal ArticleDOI
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Anne Brunet,Azad Bonni,Michael J. Zigmond,Michael Z. Lin,Peter Juo,Linda Hu,Michael J. Anderson,Karen C. Arden,John Blenis,Michael E. Greenberg +9 more
TL;DR: It is demonstrated that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors, which triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.
Journal ArticleDOI
mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery
Do Hyung Kim,Dos D. Sarbassov,Siraj M. Ali,Jessie E. King,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.
Journal ArticleDOI
Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα
Dario R. Alessi,Stephen R. James,C. Peter Downes,Andrew B. Holmes,Piers R. J. Gaffney,Colin B. Reese,Philip Cohen +6 more
TL;DR: In this paper, a protein kinase that phosphorylates PKB α at Thr308 and increases its activity over 30-fold was found to play a key role in mediating the activation of PKB by insulin and growth factors.
Journal ArticleDOI
Mechanism of activation of protein kinase B by insulin and IGF-1.
Dario R. Alessi,Mirjana Andjelkovic,Barry Caudwell,Peter Cron,Nick Morrice,Philip Cohen,Brian A. Hemmings +6 more
TL;DR: In this paper, the activation of PKBalpha was accompanied by its phosphorylation at Thr308 and Ser473 and, like activation, likeactivation was prevented by the phosphatidylinositol 3-kinase inhibitor wortmannin.
Journal ArticleDOI
Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.
Dos D. Sarbassov,Siraj M. Ali,Siraj M. Ali,Shomit Sengupta,Shomit Sengupta,Joon Ho Sheen,Joon Ho Sheen,Peggy P. Hsu,Peggy P. Hsu,Alex F. Bagley,Alex F. Bagley,Andrew L. Markhard,Andrew L. Markhard,David M. Sabatini,David M. Sabatini +14 more
TL;DR: It is shown that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolongedRapamycin treatment reduces the levels of m TORC2 below those needed to maintain Akt/PKB signaling.