Regulation of mTORC2 Signaling

Mammalian target of rapamycin (mTOR), a serine/threonine protein kinase and a master regulator of cell growth and metabolism, forms two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTORC2. While mTORC1 signaling is well characterized, mTORC2 is relatively poorly understood. mTORC2 appears to exist in functionally distinct pools, but few mTORC2 effectors/substrates have been identified. Here, we review recent advances in our understanding of mTORC2 signaling, with particular emphasis on factors that control mTORC2 activity.

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[62]  Xin Li,et al.  mTORC2 phosphorylates protein kinase Cζ to regulate its stability and activity , 2014, EMBO reports.

[63]  Wenyi Wei,et al.  Dual phosphorylation of Sin1 at T86 and T398 negatively regulates mTORC2 complex integrity and activity , 2014, Protein & Cell.

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[70]  E. Esen,et al.  WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. , 2013, Cell metabolism.

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[72]  J. Avruch,et al.  mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts. , 2013, Genes & development.

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[76]  F. Camargo,et al.  YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29 , 2012, Nature Cell Biology.

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[78]  M. Hall,et al.  Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c. , 2012, Cell metabolism.

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[85]  I. Hers,et al.  mTORC2 protein-mediated protein kinase B (Akt) serine 473 phosphorylation is not required for Akt1 activity in human platelets. , 2011, The Journal of Biological Chemistry.

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[87]  Jian Wang,et al.  mSIN1 Protein Mediates SGK1 Protein Interaction with mTORC2 Protein Complex and Is Required for Selective Activation of the Epithelial Sodium Channel* , 2011, The Journal of Biological Chemistry.

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[89]  I. Hers,et al.  mTORC2 Protein-mediated Protein Kinase B (Akt) Serine 473 Phosphorylation Is Not Required for Akt1 Activity in Human Platelets* , 2011, The Journal of Biological Chemistry.

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[95]  Chien-Hung Chen,et al.  ER Stress Inhibits mTORC2 and Akt Signaling Through GSK-3β–Mediated Phosphorylation of Rictor , 2011, Science Signaling.

[96]  Dianqing Wu,et al.  Evidence for Direct Activation of mTORC2 Kinase Activity by Phosphatidylinositol 3,4,5-Trisphosphate* , 2011, The Journal of Biological Chemistry.

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[98]  J. L. Rosa,et al.  Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling* , 2010, The Journal of Biological Chemistry.

[99]  Philippe P Roux,et al.  mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide , 2010, The EMBO journal.

[100]  N. Pavletich,et al.  Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes. , 2010, Genes & development.

[101]  A. Harwood,et al.  Glycogen Synthase Kinase-3 Is Required for Efficient Dictyostelium Chemotaxis , 2010, Molecular biology of the cell.

[102]  Hasmik Keshishian,et al.  Rictor Phosphorylation on the Thr-1135 Site Does Not Require Mammalian Target of Rapamycin Complex 2 , 2010, Molecular Cancer Research.

[103]  Tohru Natsume,et al.  Tti1 and Tel2 Are Critical Factors in Mammalian Target of Rapamycin Complex Assembly* , 2010, The Journal of Biological Chemistry.

[104]  J. Downward,et al.  Rictor is a novel target of p70 S6 kinase-1 , 2010, Oncogene.

[105]  D. Fingar,et al.  mTOR Ser-2481 Autophosphorylation Monitors mTORC-specific Catalytic Activity and Clarifies Rapamycin Mechanism of Action* , 2009, The Journal of Biological Chemistry.

[106]  Philippe P Roux,et al.  mTORC1-Activated S6K1 Phosphorylates Rictor on Threonine 1135 and Regulates mTORC2 Signaling , 2009, Molecular and Cellular Biology.

[107]  J. Asara,et al.  Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1 , 2009, Molecular and Cellular Biology.

[108]  D. Sabatini,et al.  DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival , 2009, Cell.

[109]  T. Walther,et al.  TORC2 plasma membrane localization is essential for cell viability and restricted to a distinct domain. , 2009, Molecular biology of the cell.

[110]  Gerard Manning,et al.  TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. , 2009, Cancer research.

[111]  A. Dar,et al.  The Aurora kinase A Regulates GSK-3β in Gastric Cancer Cells , 2008, Oncogene.

[112]  D. Alessi,et al.  mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). , 2008, The Biochemical journal.

[113]  Margit Rosner,et al.  Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. , 2008, Human molecular genetics.

[114]  A. Newton,et al.  The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C , 2008, The EMBO journal.

[115]  K. Inoki,et al.  Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling , 2008, The EMBO journal.

[116]  C. Collinet,et al.  The Endosomal Protein Appl1 Mediates Akt Substrate Specificity and Cell Survival in Vertebrate Development , 2008, Cell.

[117]  B. Turk,et al.  AMPK phosphorylation of raptor mediates a metabolic checkpoint. , 2008, Molecular cell.

[118]  Adiel Cohen,et al.  PRAS40 and PRR5-Like Protein Are New mTOR Interactors that Regulate Apoptosis , 2007, PloS one.

[119]  T. Griffin,et al.  PRR5, a Novel Component of mTOR Complex 2, Regulates Platelet-derived Growth Factor Receptor β Expression and Signaling* , 2007, Journal of Biological Chemistry.

[120]  D. Alessi,et al.  Identification of Protor as a novel Rictor-binding component of mTOR complex-2. , 2007, The Biochemical journal.

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[123]  A. Lipovsky,et al.  S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. , 2006, Molecular cell.

[124]  J. Qin,et al.  SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity , 2006, Cell.

[125]  Jacob D. Jaffe,et al.  mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s , 2006, Current Biology.

[126]  R. Hresko,et al.  mTOR·RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes* , 2005, Journal of Biological Chemistry.

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