Gene Symbol: Crtc2
Description: CREB regulated transcription coactivator 2
Alias: 4632407F12Rik, Torc2, CREB-regulated transcription coactivator 2, TORC-2, transducer of CREB protein 2, transducer of regulated cAMP response element-binding protein 2
Species: mouse
Products:     Crtc2

Top Publications

  1. Koo S, Flechner L, Qi L, Zhang X, Screaton R, Jeffries S, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature. 2005;437:1109-11 pubmed
    ..Here we show that hormonal and energy-sensing pathways converge on the coactivator TORC2 (transducer of regulated CREB activity 2) to modulate glucose output...
  2. Dentin R, Liu Y, Koo S, Hedrick S, Vargas T, Heredia J, et al. Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. Nature. 2007;449:366-9 pubmed
    ..fasting conditions, FOXO1 increases gluconeogenic gene expression in concert with the cAMP responsive coactivator TORC2 (refs 4-8)...
  3. Ryu D, Oh K, Jo H, Hedrick S, Kim Y, Hwang Y, et al. TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1. Cell Metab. 2009;9:240-51 pubmed publisher
    b>TORC2 is a major transcriptional coactivator for hepatic glucose production. Insulin impedes gluconeogenesis by inhibiting TORC2 via SIK2-dependent phosphorylation at Ser171...
  4. Wang Y, Inoue H, Ravnskjaer K, Viste K, Miller N, Liu Y, et al. Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity. Proc Natl Acad Sci U S A. 2010;107:3087-92 pubmed publisher
    ..pancreatic glucagon maintain glucose homeostasis through induction of gluconeogenic genes by the CREB coactivator CRTC2. Hepatic CRTC2 activity is elevated in obesity, although the extent to which this cofactor contributes to ..
  5. Miller R, Chu Q, Le Lay J, Scherer P, Ahima R, Kaestner K, et al. Adiponectin suppresses gluconeogenic gene expression in mouse hepatocytes independent of LKB1-AMPK signaling. J Clin Invest. 2011;121:2518-28 pubmed publisher
    ..Furthermore, in primary mouse hepatocytes, the absence of LKB1, AMPK, or the transcriptional coactivator CRTC2 did not prevent adiponectin from inhibiting glucose output or reducing gluconeogenic gene expression...
  6. Kumar A, Lawrence J, Jung D, Ko H, Keller S, Kim J, et al. Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism. Diabetes. 2010;59:1397-406 pubmed publisher
    ..Rictor/mTORC2 in fat cells plays an important role in whole-body energy homeostasis by mediating signaling necessary for the regulation of glucose and lipid metabolism in fat cells. ..
  7. Hallenborg P, Feddersen S, Francoz S, Murano I, Sundekilde U, Petersen R, et al. Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation. Cell Death Differ. 2012;19:1381-9 pubmed publisher
    ..of the cAMP regulatory element-binding protein (CREB) coactivator, CREB-regulated transcription coactivator (Crtc2)/TORC2, to the c/ebp? promoter...
  8. Hagiwara A, Cornu M, Cybulski N, Polak P, Betz C, Trapani F, et al. Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c. Cell Metab. 2012;15:725-38 pubmed publisher
    ..Thus, mTORC2 regulates hepatic glucose and lipid metabolism via insulin-induced Akt signaling to control whole-body metabolic homeostasis. These findings have implications for emerging drug therapies that target mTORC2. ..
  9. Jansson D, Ng A, Fu A, Depatie C, Al Azzabi M, Screaton R. Glucose controls CREB activity in islet cells via regulated phosphorylation of TORC2. Proc Natl Acad Sci U S A. 2008;105:10161-6 pubmed publisher
    ..secretion and promote synergistic CREB activity by inducing the nuclear relocalization of TORC2 (also known as Crtc2), a coactivator for CREB...

More Information


  1. García Martínez J, Alessi D. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 2008;416:375-85 pubmed publisher
    ..The results of the present study indicate that NDRG1 phosphorylation represents an excellent biomarker for mTORC2 activity. ..
  2. Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity. 2010;32:743-53 pubmed publisher
    ..Collectively, the data uncover vital mTOR-PKC and mTOR-Akt connections in T cell differentiation and reveal distinct pathways by which mTORC2 regulates development of Th1 and Th2 cell subsets. ..
  3. Wang Y, Vera L, Fischer W, Montminy M. The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis. Nature. 2009;460:534-7 pubmed publisher
    ..mammals, circulating pancreatic glucagon stimulates hepatic gluconeogenesis in part through the CREB regulated transcription coactivator 2 (CRTC2, also referred to as TORC2)...
  4. Park J, Yoon Y, Han H, Kim Y, Ogawa Y, Park K, et al. SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo. Diabetes. 2014;63:3659-73 pubmed publisher
    ..Interestingly, SIK2 KO promoted the enhancement in the CRTC2-CREB transcriptional pathway in white adipocytes...
  5. Yang Q, Inoki K, Ikenoue T, Guan K. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev. 2006;20:2820-32 pubmed
    ..TOR exists in two distinct complexes, termed TORC1 and TORC2. Mammalian TORC2 has recently been shown to possess kinase activity toward the C-terminal hydrophobic site of Akt/..
  6. Hernandez J, Chang C, Leblanc M, Grimm D, Le Lay J, Kaestner K, et al. The CREB/CRTC2 pathway modulates autoimmune disease by promoting Th17 differentiation. Nat Commun. 2015;6:7216 pubmed publisher
    ..Here we show that PGE2 enhances Th17 cell differentiation via the activation of the CREB co-activator CRTC2. Following its dephosphorylation, CRTC2 stimulates the expression of the cytokines IL-17A and IL-17F by binding to ..
  7. Ravnskjaer K, Hogan M, Lackey D, Tora L, Dent S, Olefsky J, et al. Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects. J Clin Invest. 2013;123:4318-28 pubmed publisher
    ..phosphorylation of cAMP response element-binding protein (CREB) and the dephosphorylation of the CREB coactivator CRTC2. Hormonal and nutrient signals are also thought to modulate gluconeogenic gene expression by promoting epigenetic ..
  8. Mansley M, Wilson S. Dysregulation of epithelial Na+ absorption induced by inhibition of the kinases TORC1 and TORC2. Br J Pharmacol. 2010;161:1778-92 pubmed publisher
    ..As SGK1 activity is dependent upon target of rapamycin complex 2 (TORC2)-catalysed phosphorylation of SGK1-Ser(422) , we have explored the effects of inhibiting TORC2 and/or TORC1 upon ..
  9. Muraoka M, Fukushima A, Viengchareun S, Lombes M, Kishi F, Miyauchi A, et al. Involvement of SIK2/TORC2 signaling cascade in the regulation of insulin-induced PGC-1alpha and UCP-1 gene expression in brown adipocytes. Am J Physiol Endocrinol Metab. 2009;296:E1430-9 pubmed publisher
    ..protein (CREB)-mediated gene expression by phosphorylating the coactivator transducer of regulated CREB activity (TORC2). Phosphorylation at Ser(587) of SIK2 diminishes its TORC2 phosphorylation activity...
  10. Saci A, Cantley L, Carpenter C. Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size. Mol Cell. 2011;42:50-61 pubmed publisher
    ..Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously. ..
  11. Goncharova E, Goncharov D, Li H, Pimtong W, Lu S, Khavin I, et al. mTORC2 is required for proliferation and survival of TSC2-null cells. Mol Cell Biol. 2011;31:2484-98 pubmed publisher
  12. Kaur S, Sassano A, Majchrzak Kita B, Baker D, Su B, Fish E, et al. Regulatory effects of mTORC2 complexes in type I IFN signaling and in the generation of IFN responses. Proc Natl Acad Sci U S A. 2012;109:7723-8 pubmed publisher
    ..Together, our data provide evidence for unique functions of mTORC2 complexes in the induction of type I IFN responses and suggest a critical role for mTORC2-mediated signals in IFN signaling. ..
  13. Luan B, Goodarzi M, Phillips N, Guo X, Chen Y, Yao J, et al. Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4. Cell Metab. 2014;19:1058-65 pubmed publisher
  14. Fort P, Losiewicz M, Pennathur S, Jefferson L, Kimball S, ABCOUWER S, et al. mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes. Diabetes. 2014;63:3077-90 pubmed publisher
    ..These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. ..
  15. Lerner R, Depatie C, Rutter G, Screaton R, Balthasar N. A role for the CREB co-activator CRTC2 in the hypothalamic mechanisms linking glucose sensing with gene regulation. EMBO Rep. 2009;10:1175-81 pubmed publisher
    ..the cyclic AMP-response element binding protein (CREB) co-activator CREB-regulated transcription co-activator 2 (CRTC2) in maintaining glucose homeostasis has been shown in the liver...
  16. Li Y, Song Y, Zhao M, Guo Y, Yu C, Chen W, et al. A novel role for CRTC2 in hepatic cholesterol synthesis through SREBP-2. Hepatology. 2017;66:481-497 pubmed publisher
    ..However, the effect of CRTC2 on cholesterol and its potential molecular mechanism remain unclear...
  17. Shaw R, Lamia K, Vasquez D, Koo S, Bardeesy N, Depinho R, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310:1642-6 pubmed
    ..In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered ..
  18. Angliker N, Ruegg M. In vivo evidence for mTORC2-mediated actin cytoskeleton rearrangement in neurons. Bioarchitecture. 2013;3:113-8 pubmed publisher
  19. Colombi M, Molle K, Benjamin D, Rattenbacher Kiser K, Schaefer C, Betz C, et al. Genome-wide shRNA screen reveals increased mitochondrial dependence upon mTORC2 addiction. Oncogene. 2011;30:1551-65 pubmed publisher
    ..We conclude that mTORC2-addicted cells require mitochondrial functions that may be novel drug targets in human cancer. ..
  20. Ohmae S, Takemoto Kimura S, Okamura M, Adachi Morishima A, Nonaka M, Fuse T, et al. Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV. J Biol Chem. 2006;281:20427-39 pubmed
    ..transcription, we here show that CL1 and CL2 were unable to significantly phosphorylate CREB Ser-133 and rather inhibited CRE-dependent gene expression by a dominant mechanism that bypassed CREB and was mediated by phosphorylated TORC2.
  21. Ryder E, Gleeson D, Sethi D, Vyas S, Miklejewska E, Dalvi P, et al. Molecular characterization of mutant mouse strains generated from the EUCOMM/KOMP-CSD ES cell resource. Mamm Genome. 2013;24:286-94 pubmed publisher
  22. Matheny R, Lynch C, Leandry L. Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110?-deficient myoblasts is mediated by PI3K p110? and mTORC2. Growth Factors. 2012;30:367-84 pubmed publisher
    ..These data demonstrate that reductions in p110? are associated with agonist-specific Akt hyperactivation and accelerated myogenesis, thus revealing a negative role for p110? in Akt activation and during myoblast differentiation. ..
  23. Lamming D, Mihaylova M, Katajisto P, Baar E, Yilmaz O, Hutchins A, et al. Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan. Aging Cell. 2014;13:911-7 pubmed publisher
    ..Our results suggest that inhibition of mTORC2 signaling is detrimental to males, which may explain in part why interventions that decrease mTOR signaling show greater efficacy in females. ..
  24. Sonntag T, Moresco J, Vaughan J, Matsumura S, Yates J, Montminy M. Analysis of a cAMP regulated coactivator family reveals an alternative phosphorylation motif for AMPK family members. PLoS ONE. 2017;12:e0173013 pubmed publisher
    ..exhibit distinct patterns of 14-3-3 binding at three conserved sites corresponding to S70, S171, and S275 (in CRTC2)...
  25. Shen Q, Stanton M, Feng W, Rodriguez M, Ramondetta L, Chen L, et al. Morphoproteomic analysis reveals an overexpressed and constitutively activated phospholipase D1-mTORC2 pathway in endometrial carcinoma. Int J Clin Exp Pathol. 2010;4:13-21 pubmed
  26. Sciarretta S, Zhai P, Maejima Y, Del Re D, Nagarajan N, Yee D, et al. mTORC2 regulates cardiac response to stress by inhibiting MST1. Cell Rep. 2015;11:125-36 pubmed publisher
    ..In conclusion, our study demonstrates the existence of a direct crosstalk between mTORC2 and MST1 that is critical for cardiac cell survival and growth. ..
  27. Humphrey S, Yang G, Yang P, Fazakerley D, Stöckli J, Yang J, et al. Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2. Cell Metab. 2013;17:1009-20 pubmed publisher
    ..The dynamic phosphoproteome described here contains numerous phosphorylation sites on proteins involved in diverse molecular functions and should serve as a useful functional resource for cell biologists. ..
  28. Wu D, Yu D, Wang X, Yu B. F-actin rearrangement is regulated by mTORC2/Akt/Girdin in mouse fertilized eggs. Cell Prolif. 2016;49:740-750 pubmed publisher
    ..Collectively, this study aimed to prove the participation of mTORC2/Akt in F-actin assembling in early-stage cleavage of mouse fertilized eggs via the function of Girdin. ..
  29. Bruno N, Kelly K, Hawkins R, Bramah Lawani M, Amelio A, Nwachukwu J, et al. Creb coactivators direct anabolic responses and enhance performance of skeletal muscle. EMBO J. 2014;33:1027-43 pubmed publisher
    ..intense exercise induce Creb-mediated transcriptional programs through activation of its obligate coactivators Crtc2 and Crtc3...
  30. Kaska S, Brunk R, Bali V, Kechner M, Mazei Robison M. Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior. Neuropharmacology. 2017;117:158-170 pubmed publisher
    ..In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of ..
  31. Martin T, Dennis M, Gordon B, Kimball S, Jefferson L. mTORC1 and JNK coordinate phosphorylation of the p70S6K1 autoinhibitory domain in skeletal muscle following functional overloading. Am J Physiol Endocrinol Metab. 2014;306:E1397-405 pubmed publisher
    ..Overall, the results provide evidence that the mTORC1 and JNK signaling pathways coordinate the site-specific phosphorylation of p70S6K1. They also identify a novel role for mTORC1 and mTORC2 in the inhibition of JNK. ..
  32. Hallenborg P, Siersbæk M, Barrio Hernandez I, Nielsen R, Kristiansen K, Mandrup S, et al. MDM2 facilitates adipocyte differentiation through CRTC-mediated activation of STAT3. Cell Death Dis. 2016;7:e2289 pubmed publisher
    ..Moreover, STATs were able to interact with the transcriptional cofactors CRTC2 and CRTC3, hitherto only reported to associate with the cAMP-responsive transcription factor CREB...
  33. Wu Y, Ouyang W, Lazorchak A, Liu D, Shen H, Su B. mTOR complex 2 targets Akt for proteasomal degradation via phosphorylation at the hydrophobic motif. J Biol Chem. 2011;286:14190-8 pubmed publisher
    ..Taken together, this study reveals that the Akt Ser-473 phosphorylation-dependent ubiquitination and degradation is an important negative feedback regulation that specifically terminates Akt activation. ..
  34. Han H, Jung C, Yoon Y, Choi S, Choi D, Kang G, et al. Arginine methylation of CRTC2 is critical in the transcriptional control of hepatic glucose metabolism. Sci Signal. 2014;7:ra19 pubmed publisher
    ..gluconeogenesis by the transcription factor CREB (cAMP response element-binding protein) and its coactivator CRTC2 (CREB-regulated transcriptional coactivator 2)...
  35. Eberhard C, Fu A, Reeks C, Screaton R. CRTC2 is required for ?-cell function and proliferation. Endocrinology. 2013;154:2308-17 pubmed publisher
    ..Here, we report that Crtc2 is essential both for glucose-stimulated insulin secretion and cell survival in the ?-cell...
  36. Han H, Choi B, Kim J, Kang G, Koo S. Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis. Nat Commun. 2017;8:1878 pubmed publisher
    ..b>Crtc2 liver-specific knockout lowers blood glucose levels with improved glucose and insulin tolerance...
  37. Dullea R, Salatto C, Sciabola S, Chen T, Dimattia D, Gandhok H, et al. Study of CRTC2 pharmacology using antisense oligonuceotides. Nucleic Acid Ther. 2014;24:127-38 pubmed publisher
    The cAMP response element binding protein (CREB)-regulated transcriptional coactivator 2 (CRTC2) is a key component of the transcription complex regulating glucagon driven hepatic glucose production and previous evidence suggests that &..
  38. Chen Z, Kang X, Wang L, Dong H, Wang C, Xiong Z, et al. Rictor/mTORC2 pathway in oocytes regulates folliculogenesis, and its inactivation causes premature ovarian failure. J Biol Chem. 2015;290:6387-96 pubmed publisher
    ..Our results collectively indicate key roles of Rictor/mTORC2 in folliculogenesis, follicle survival, and female fertility and support the utility of oocyte-specific Rictor knock-out mice as a novel model for POF. ..
  39. Partovian C, Ju R, Zhuang Z, Martin K, Simons M. Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells. Mol Cell. 2008;32:140-9 pubmed publisher
    ..Thus, S4-dependent targeting of PKCalpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation. ..
  40. Hagan G, Lin Y, Magnuson M, Avruch J, Czech M. A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes. Mol Cell Biol. 2008;28:4215-26 pubmed publisher
    ..Taken together, our findings suggest that the Rictor-Myo1c complex is distinct from mTORC2 and that Myo1c, in conjunction with Rictor, participates in cortical actin remodeling events. ..
  41. Devi L, Ohno M. PERK mediates eIF2? phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer's disease. Neurobiol Aging. 2014;35:2272-81 pubmed publisher
    ..Together, these findings suggest that PERK may be a disease-modifying therapeutic target to prevent multiple memory-disrupting mechanisms associated with AD. ..
  42. Luan B, Yoon Y, Le Lay J, Kaestner K, Hedrick S, Montminy M. CREB pathway links PGE2 signaling with macrophage polarization. Proc Natl Acad Sci U S A. 2015;112:15642-7 pubmed publisher
    ..Targeted disruption of CREB or the cAMP-regulated transcriptional coactivators 2 and 3 (CRTC2/3) in macrophages down-regulated M2 marker gene expression and promoted insulin resistance in the context of high-..
  43. Wang R, Kim H, Xiao C, Xu X, Gavrilova O, Deng C. Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Invest. 2011;121:4477-90 pubmed publisher
    ..These data delineate a pathway through which Sirt1 maintains insulin sensitivity and suggest that treatment with antioxidants might provide protection against progressive insulin resistance in older human populations. ..
  44. Han J, Li E, Chen L, Zhang Y, Wei F, Liu J, et al. The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1. Nature. 2015;524:243-6 pubmed publisher
    ..Here we show in mice that CREB regulated transcription coactivator 2 (CRTC2) functions as a mediator of mTOR signalling to modulate COPII-dependent SREBP1 processing...
  45. Le Lay J, Tuteja G, White P, Dhir R, Ahima R, Kaestner K. CRTC2 (TORC2) contributes to the transcriptional response to fasting in the liver but is not required for the maintenance of glucose homeostasis. Cell Metab. 2009;10:55-62 pubmed publisher
    ..We derived CRTC2 (CREB-regulated transcription coactivator 2, previously TORC2)-deficient mice to assess the contribution of this cofactor to hepatic glucose metabolism in vivo...
  46. Johnson J, Huang W, Roman G, Costa Mattioli M. TORC2: a novel target for treating age-associated memory impairment. Sci Rep. 2015;5:15193 pubmed publisher
    ..These insights into the molecular basis of age-related memory loss may hold promise for new treatments for cognitive disorders. ..
  47. Sen B, Xie Z, Case N, Thompson W, Uzer G, Styner M, et al. mTORC2 regulates mechanically induced cytoskeletal reorganization and lineage selection in marrow-derived mesenchymal stem cells. J Bone Miner Res. 2014;29:78-89 pubmed publisher
    ..As such, mechanical activation of mTORC2 signaling participates in mesenchymal stem cell lineage selection, preventing adipogenesis by preserving ?-catenin and stimulating osteogenesis by generating a stiffer cytoskeleton. ..
  48. Dentin R, Hedrick S, Xie J, Yates J, Montminy M. Hepatic glucose sensing via the CREB coactivator CRTC2. Science. 2008;319:1402-5 pubmed publisher
    ..of the transducer of regulated cyclic adenosine monophosphate response element-binding protein (CREB) 2 (TORC2 or CRTC2)...
  49. Hogan M, Ravnskjaer K, Matsumura S, Huising M, Hull R, Kahn S, et al. Hepatic Insulin Resistance Following Chronic Activation of the CREB Coactivator CRTC2. J Biol Chem. 2015;290:25997-6006 pubmed publisher
    ..program via the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP-regulated CREB coactivators CRTC2 and CRTC3...
  50. Yano T, Ferlito M, Aponte A, Kuno A, Miura T, Murphy E, et al. Pivotal role of mTORC2 and involvement of ribosomal protein S6 in cardioprotective signaling. Circ Res. 2014;114:1268-80 pubmed publisher
    ..Activation of mTORC2 plays a pivotal role in cardioprotection, and Rps6 is a convergence point of cardioprotective signaling, providing positive feedback regulation of mTORC2/Akt signaling. ..
  51. Wahane S, Hellbach N, Prentzell M, Weise S, Vezzali R, Kreutz C, et al. PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2. J Neurochem. 2014;130:255-67 pubmed publisher
    ..PI3K-p110-beta-signalling activates a different mTORC2. Both PI3K/mTORC2-signalling pathways are required but not directly activated in TGF?-mediated neuronal differentiation. ..
  52. Hasumi Y, Baba M, Ajima R, Hasumi H, Valera V, Klein M, et al. Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci U S A. 2009;106:18722-7 pubmed publisher
  53. Lee J, Tong T, Takemori H, Jefcoate C. Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB. Mol Cell Endocrinol. 2015;408:80-9 pubmed publisher
    ..processing, which are synchronized by salt inducible kinase (SIK1) and CREB-regulated transcription coactivator (CRTC2)...
  54. Zhang C, Wendel A, Keogh M, Harris T, Chen J, Coleman R. Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling. Proc Natl Acad Sci U S A. 2012;109:1667-72 pubmed publisher
    ..These data demonstrate a critical link between nutrient excess, TAG synthesis, and hepatic insulin resistance. ..
  55. Wang Y, Li G, Goode J, Paz J, Ouyang K, Screaton R, et al. Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes. Nature. 2012;485:128-32 pubmed publisher
    ..the cyclic AMP pathway increases gluconeogenic gene expression via the de-phosphorylation of the CREB co-activator CRTC2 (ref. 1)...
  56. Erion D, Kotas M, McGlashon J, Yonemitsu S, Hsiao J, Nagai Y, et al. cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) promotes glucagon clearance and hepatic amino acid catabolism to regulate glucose homeostasis. J Biol Chem. 2013;288:16167-76 pubmed publisher
    cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) regulates transcription of gluconeogenic genes by specifying targets for the transcription factor CREB in response to glucagon...
  57. Shu L, Houghton P. The mTORC2 complex regulates terminal differentiation of C2C12 myoblasts. Mol Cell Biol. 2009;29:4691-700 pubmed publisher
    ..Importantly, downregulation of rictor inhibited TORC2 signaling without inhibiting mTORC1 signaling, suggesting that inhibition of mTORC1 by rapamycin may not be the ..
  58. Woo J, Kang S. Diet change and exercise enhance protein expression of CREB, CRTC 2 and lipolitic enzymes in adipocytes of obese mice. Lipids Health Dis. 2016;15:147 pubmed publisher
    ..Change in diet in the absence of exercise was not associated with changes in adipose tissue CRTC family lipase activity, indicating that lipolysis metabolic processes are effective only when diet and exercise are carried out together. ..
  59. Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Horike N, et al. Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing cAMP-responsive element transcriptional activity. J Biol Chem. 2010;285:33018-27 pubmed publisher
    ..Herein, we identified CRTC2 as a Pin1-binding protein by overexpressing Pin1 with Myc and FLAG tags in mouse livers and subsequent ..
  60. Raïch Regué D, Rosborough B, Watson A, McGeachy M, Turnquist H, Thomson A. mTORC2 Deficiency in Myeloid Dendritic Cells Enhances Their Allogeneic Th1 and Th17 Stimulatory Ability after TLR4 Ligation In Vitro and In Vivo. J Immunol. 2015;194:4767-76 pubmed publisher
    ..Our findings provide new insight into the role of mTORC2 in regulating DC function and may have implications for emerging therapeutic strategies that target mTOR in cancer, infectious diseases, and transplantation. ..
  61. Destefano M, Jacinto E. Regulation of insulin receptor substrate-1 by mTORC2 (mammalian target of rapamycin complex 2). Biochem Soc Trans. 2013;41:896-901 pubmed publisher
    ..Our findings reveal that, in addition to persistent mTORC1 signalling, increased mTORC2 signals can promote insulin resistance due to mTORC2-mediated degradation of IRS-1. ..
  62. Dibble C, Asara J, Manning B. Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol. 2009;29:5657-70 pubmed publisher
    ..We provide evidence that Rictor-T1135 phosphorylation acts in parallel with other mTORC1-dependent feedback mechanisms, such as those affecting IRS-1 signaling to PI3K, to regulate the response of Akt to insulin. ..
  63. Völkers M, Konstandin M, Doroudgar S, Toko H, Quijada P, Din S, et al. Mechanistic target of rapamycin complex 2 protects the heart from ischemic damage. Circulation. 2013;128:2132-44 pubmed publisher
    ..These results suggest that selectively increasing mTORC2 while concurrently inhibiting mTORC1 signaling is a novel therapeutic approach for the treatment of ischemic heart disease. ..
  64. Wang Y, Weiss L, Orlofsky A. Coordinate control of host centrosome position, organelle distribution, and migratory response by Toxoplasma gondii via host mTORC2. J Biol Chem. 2010;285:15611-8 pubmed publisher
  65. Carr T, Feehan R, Hall M, Rüegg M, Shantz L. Conditional disruption of rictor demonstrates a direct requirement for mTORC2 in skin tumor development and continued growth of established tumors. Carcinogenesis. 2015;36:487-97 pubmed publisher
  66. Blanchet E, Van de Velde S, Matsumura S, Hao E, LeLay J, KAESTNER K, et al. Feedback inhibition of CREB signaling promotes beta cell dysfunction in insulin resistance. Cell Rep. 2015;10:1149-57 pubmed publisher
    ..Here, we show that mice with a knockout of the CREB coactivator CRTC2 in beta cells have impaired oral glucose tolerance due to decreases in circulating insulin concentrations...
  67. Seok S, Fu T, Choi S, Li Y, Zhu R, Kumar S, et al. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature. 2014;516:108-11 pubmed publisher
    ..Mechanistically, CREB upregulated autophagy genes, including Atg7, Ulk1 and Tfeb, by recruiting the coactivator CRTC2. After feeding or pharmacological activation, FXR trans-repressed these genes by disrupting the functional CREB-..
  68. Jiang S, Inada T, Tanaka M, Furuta R, Shingu K, Fujisawa J. Involvement of TORC2, a CREB co-activator, in the in vivo-specific transcriptional control of HTLV-1. Retrovirology. 2009;6:73 pubmed publisher
    ..However, the expression of TORC2, a co-activator of CREB, decreased substantially in the EL4-Gax cells in vivo, and this returned to normal levels ..
  69. Perkey E, Fingar D, Miller R, Garcia G. Increased mammalian target of rapamycin complex 2 signaling promotes age-related decline in CD4 T cell signaling and function. J Immunol. 2013;191:4648-55 pubmed publisher
    ..the mammalian target of rapamycin (TOR) has been implicated in aging, the roles of the TOR complexes (TORC1, TORC2) in the functional declines of CD4 T cells remain unknown...
  70. Boulbes D, Chen C, Shaikenov T, Agarwal N, Peterson T, Addona T, et al. Rictor phosphorylation on the Thr-1135 site does not require mammalian target of rapamycin complex 2. Mol Cancer Res. 2010;8:896-906 pubmed publisher
    ..We found that this rictor phosphorylation takes place in the mTORC2-deficient cells, suggesting that this modification might play a role in the regulation of not only mTORC2 but also the mTORC2-independent function of rictor. ..
  71. Gan X, Wang J, Wang C, Sommer E, Kozasa T, Srinivasula S, et al. PRR5L degradation promotes mTORC2-mediated PKC-? phosphorylation and cell migration downstream of G?12. Nat Cell Biol. 2012;14:686-96 pubmed publisher
    ..This G?(12)-mediated signalling pathway for mTORC2 regulation is critically important for fibroblast migration and pulmonary fibrosis development. ..
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    ..Our study demonstrates that mTORC2 is implicated in maintaining contractile function of the pressure-overloaded male mouse heart. ..
  73. Albert V, Svensson K, Shimobayashi M, Colombi M, Muñoz S, Jimenez V, et al. mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue. EMBO Mol Med. 2016;8:232-46 pubmed publisher
    ..Thus, mTORC2 in BAT mediates temperature homeostasis via regulation of cold-induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation. ..
  74. Jeanneteau F, Lambert W, Ismaili N, Bath K, Lee F, Garabedian M, et al. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus. Proc Natl Acad Sci U S A. 2012;109:1305-10 pubmed publisher
    ..We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.
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    ..Taken together, our results suggest a role for mTORC2 in the inflammatory-oxidative responses to stress. ..
  76. Lee K, Nam K, Cho S, Gudapati P, Hwang Y, Park D, et al. Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia. J Exp Med. 2012;209:713-28 pubmed publisher
    ..Collectively, these findings reveal roles for mTORC2 in promoting thymic T cell development and T-ALL and indicate that mTORC2 is crucial for Notch signaling to regulate Akt and NF-?B. ..
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    ..These data support the conclusion that mTORC2 uses distinct strategies to phosphorylate different substrates and suggest a mechanism for mTORC2 specificity in the regulation of diverse cellular processes. ..