Gene interactions and pathways from curated databases and text-mining

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MTOR — RICTOR

Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Audhya et al., EMBO J 2004 : Consistent with these findings, phosphorylation of Slm1 and Slm2 was dependent on TORC2 protein kinase activity, both in vivo and in vitro, and Slm1 localization required both PI4,5P ( 2 ) and functional TORC2 ... Consistent with these findings, phosphorylation of Slm1 and Slm2 was dependent on TORC2 protein kinase activity, both in vivo and in vitro, and Slm1 localization required both PI4,5P ( 2 ) and functional TORC2
Canettieri et al., Cell Metab 2005 : Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling ... Here, we show that, in parallel with their effects on glucose output, CREB and TORC2 also enhance insulin signaling in liver by stimulating expression of the insulin receptor substrate 2 (IRS2) gene
Sarbassov et al., Mol Cell 2006 : mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival ... mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival
Yang et al., Proc Natl Acad Sci U S A 2006 : We also observed that Rheb does not activate TORC2 in human embryonic kidney 293 cells, although it potently stimulates TORC1
Ohmae et al., J Biol Chem 2006 : Although these were previously shown to activate Ca ( 2+ ) /cAMP-response element binding protein ( CREB ) -dependent 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
Guertin et al., Dev Cell 2006 : Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKCalpha pathways
Zeng et al., Blood 2007 (Leukemia, Myeloid, Acute) : Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
Hietakangas et al., Genes Dev 2007 : Here we analyze the role of TORC2 mediated AKT phosphorylation in Drosophila
Kuraishy et al., Proc Natl Acad Sci U S A 2007 (Cell Transformation, Neoplastic) : Here we show that the CREB coactivator TORC2 directly regulates TCL1 expression independent of CREB Ser-133 phosphorylation and CBP/p300 recruitment
Woo et al., J Biol Chem 2007 (Breast Neoplasms...) : Despite no significant effect of PRR5 on mTORC2 mediated Akt phosphorylation, PRR5 silencing inhibits Akt and S6K1 phosphorylation and reduces cell proliferation rates, a result consistent with PRR5 roles in cell growth and tumorigenesis
Dentin et al., Nature 2007 (Diabetes Mellitus) : Insulin disrupts TORC2 activity by induction of the Ser/Thr kinase SIK2, which we show here undergoes AKT2 mediated phosphorylation at Ser 358 ... Activated SIK2 in turn stimulated the Ser 171 phosphorylation and cytoplasmic translocation of TORC2
Kumar et al., Mol Cell Biol 2008 : Since little is known about the role of either rictor or mTORC2 in PI-3 kinase mediated physiological processes in adult animals, we generated muscle-specific rictor knockout mice
Amelio et al., Proc Natl Acad Sci U S A 2007 : Furthermore, TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts as a bridge between the CREB/TORC complex and RNA polymerase II
Kim et al., Mol Cell Biol 2008 : Subsequent studies established that GIP increased the nuclear localization of TORC2 and phosphorylation of CREB serine 133 through a pathway involving PKA activation and reduced AMPK phosphorylation ... The antiapoptotic effect of GIP in beta cells is therefore partially mediated through a novel mode of transcriptional regulation of Bcl-2 involving cAMP/PKA/AMPK dependent regulation of CREB/TORC2 activity ... The antiapoptotic effect of GIP in beta cells is therefore partially mediated through a novel mode of transcriptional regulation of Bcl-2 involving cAMP/PKA/AMPK dependent regulation of CREB/TORC2 activity
Masri et al., Cancer Res 2007 (Brain Neoplasms...) : mTORC2 has recently been shown to phosphorylate and activate Akt
Dickson et al., J Lipid Res 2008 (Inflammation) : Advances in understanding how the de novo synthesis of ceramide and complex sphingolipids is regulated have been made, and they demonstrate that the Target Of Rapamycin Complex 2 (TORC2) controls ceramide synthase activity ... The activity of Slm1 and Slm2 has also been shown to be regulated during heat stress by phosphoinositides and TORC2 , along with sphingoid long-chain bases and the Pkh1 and Pkh2 protein kinases, to control the actin cytoskeleton, the trafficking of nutrient transporters, and cell viability ... The activity of Slm1 and Slm2 has also been shown to be regulated during heat stress by phosphoinositides and TORC2 , along with sphingoid long-chain bases and the Pkh1 and Pkh2 protein kinases, to control the actin cytoskeleton, the trafficking of nutrient transporters, and cell viability
Huang et al., Mol Cell Biol 2008 : However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown ... Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase activating protein activity toward Rheb ... These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2 , which through different mechanisms promotes Akt activation
Kamimura et al., Curr Biol 2008 : Here, we outline a PIP ( 3 ) -independent pathway linking temporal and spatial activation of PKBs by Tor complex 2 (TorC2) to the chemotactic response
Wang et al., Oncogene 2008 (Prostatic Neoplasms) : Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2 ... Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2 ... Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1 , but not mTORC2
Wang et al., Cancer Res 2008 (Lung Neoplasms) : The present work focused on addressing the role of mTOR/rictor in mTOR inhibitor induced Akt activation and the effect of sustained Akt activation on mTOR targeted cancer therapy
Lishner et al., Cell Signal 2008 (Multiple Myeloma) : Herein we demonstrate that the anti-myeloma effect of CD81/CD82 involves a down-regulation of Akt, activation of FoxO transcription factors and a decrease in active mTOR and mTOR/rictor ... Herein we demonstrate that the anti-myeloma effect of CD81/CD82 involves a down-regulation of Akt, activation of FoxO transcription factors and a decrease in active mTOR and mTOR/rictor
Hietakangas et al., BMC cancer 2008 (Breast Neoplasms...) : TOR complex 2 (TORC2) activates AKT by phosphorylating it on the ` hydrophobic motif ' site
Partovian et al., Mol Cell 2008 : Reduced mTORC2 activity in S4 ( -/- ) endothelial cells results in decreased FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4 ( -/- ) mice ... Reduced mTORC2 activity in S4 ( -/- ) endothelial cells results in decreased FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4 ( -/- ) mice
Toschi et al., J Biol Chem 2008 : These data indicate that although HIF1 alpha is dependent on both mTORC1 and mTORC2, HIF2 alpha is dependent only on mTORC2 ... These data indicate that although HIF1 alpha is dependent on both mTORC1 and mTORC2 , HIF2 alpha is dependent only on mTORC2
Dormond et al., J Immunol 2008 (Inflammation...) : CD40 induced signaling in human endothelial cells results in mTORC2- and Akt dependent expression of vascular endothelial growth factor in vitro and in vivo
Bentzinger et al., Cell Metab 2008 (Muscular Dystrophies) : Finally, we show that activation of PKB/Akt does not require mTORC2 ... Finally, we show that activation of PKB/Akt does not require mTORC2
Rahimi et al., Cancer Res 2009 : mTORC2 promotes TGF-beta induced morphologic transformation and is required for TGF-beta induced Akt S473 phosphorylation but not mTORC1 activation
Werzowa et al., Br J Dermatol 2009 (Melanoma...) : Inhibition of mTORC2 led to reduced levels of phosphorylated AKT
Balasubramanian et al., Cardiovasc Hematol Agents Med Chem 2009 (Cardiomegaly) : mTORC2 regulates the actin cytoskeleton in addition to activating Akt ( Protein kinase B ) for the subsequent removal of proapoptotic factors via the UPS for cell survival
Ryu et al., Cell Metab 2009 (Glucose Intolerance...) : TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1
Jones et al., PLoS Biol 2009 : These findings identify new physiological roles for TORC2 , mediated by SGK , in regulation of C. elegans lipid accumulation and growth, and they challenge the notion that AKT is the primary effector of TORC2 function
Lodeiro et al., PloS one 2009 : This beta-arrestin scaffolded complex leads to full activation of Akt through PDK1 and mTORC2 , which are not associated to the complex
Wang et al., Science signaling 2009 (Cardiovascular Diseases...) : Rapamycin treatment of diet induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke
Bozulic et al., Curr Opin Cell Biol 2009 (Neoplasms) : This present review concerns PKB regulation by mTORC2 and DNA-PK in a stimulus dependent and context dependent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention
Peterson et al., Cell 2009 (Multiple Myeloma) : Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities
Cybulski et al., Proc Natl Acad Sci U S A 2009 (Fatty Liver) : mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB ... mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB
Wang et al., J Biol Chem 2009 : Inhibition of mTORC1 or mTORC2 by transiently or moderately activated MEK/ERK caused moderately enhanced Beclin 1 resulting in cytoprotective autophagy, whereas inhibition of both mTORC1 and mTORC2 by sustained MEK/ERK activation caused strongly pronounced Beclin 1 leading to cytodestructive autophagy
Zhang et al., PloS one 2009 : Loss of function of the TSC1-TSC2 complex results in constitutive mTORC1 signaling and, through mTORC1 dependent feedback mechanisms and loss of mTORC2 activity, leads to a concomitant block of Akt signaling to its other downstream targets
Huang et al., Cancer Res 2009 (Angiomyolipoma...) : We also show that the TSC1-TSC2 complex can directly stimulate the in vitro kinase activity of mTORC2
Dibble et al., Mol Cell Biol 2009 : Although this phosphorylation event does not affect mTORC2 integrity or in vitro kinase activity, expression of a phosphorylation site mutant of Rictor ( T1135A ) in either wild-type or Rictor null cells causes an increase in the mTORC2 dependent phosphorylation of Akt on S473 ... However, Rictor-T1135 phosphorylation does not appear to regulate mTORC2 mediated effects on SGK1 or PKC alpha ... However, Rictor-T1135 phosphorylation does not appear to regulate mTORC2 mediated effects on SGK1 or PKC alpha
Boletta et al., PathoGenetics 2009 : The mTORC1 complex regulates cell growth ( size ), proliferation, translation and autophagy, and mTORC2 regulates the actin cytoskeleton and apoptosis
Koike-Kumagai et al., EMBO J 2009 : Moreover, TORC2 is essential for Trc phosphorylation on a residue that is critical for Trc activity in vivo and in vitro
Treins et al., Oncogene 2010 : Rictor phosphorylation at Thr1135 does not lead to major changes in mTORC2-kinase activity
Gurusamy et al., Cardiovasc Res 2010 : Although resveratrol attenuated the activation of mTOR complex 1, low-dose resveratrol significantly induced the expression of Rictor , a component of mTOR complex 2, and activated its downstream survival kinase Akt ( Ser 473 )
Julien et al., Mol Cell Biol 2010 : While mTOR complex 1 (mTORC1) regulates mRNA translation and ribosome biogenesis, mTORC2 plays an important role in the phosphorylation and subsequent activation of Akt ... We found that Rictor phosphorylation requires mTORC1 activity and, more specifically, the p70 ribosomal S6 kinase 1 ( S6K1 ) ... However, cells expressing a Rictor T1135A mutant were found to have increased mTORC2 dependent phosphorylation of Akt ... In addition, phosphorylation of the Akt substrates FoxO1/3a and glycogen synthase kinase 3 alpha/beta ( GSK3 alpha/beta ) was found to be increased in these cells, indicating that S6K1 mediated phosphorylation of Rictor inhibits mTORC2 and Akt signaling
Kim et al., J Biol Chem 2010 (Breast Neoplasms...) : In contrast, API-1 had no effects on the activities of the upstream Akt activators, phosphatidylinositol 3-kinase, phosphatidylinositol dependent kinase-1, and mTORC2
Yu et al., Cancer Res 2010 (Neoplasms) : Importantly, consistent with genetic ablation of mTORC2, WYE-132 targeted P-AKT ( S473 ) and AKT function without significantly reducing the steady-state level of the PI3K/PDK1 activity biomarker P-AKT ( T308 ), highlighting a prominent and direct regulation of AKT by mTORC2 in cancer cells
Yang et al., Cell cycle (Georgetown, Tex.) 2010 (Neoplasms) : Akt activity is well-known regulated through its phosphorylation at T308 and S473 by PDK1 and mTOrC2 , respectively
Liao et al., J Cell Sci 2010 : Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1 requires separate but coordinated functions of PDK1 and TORC2
Kumar et al., Diabetes 2010 : To determine the physiological role of rictor/mTORC2 in insulin signaling and action in fat cells, we developed fat cell-specific rictor knockout ( FRic ( -/- ) ) mice
Sini et al., Autophagy 2010 (Neoplasms) : mTORC2 activates AKT directly by phosphorylating Serine 473
Lyo et al., Biochem Biophys Res Commun 2010 (Kidney Neoplasms) : We report here that the PLD/mTOR dependent stabilization of HDM2 involves mTORC2 and the AGC family kinase serum- and glucocorticoid-inducible kinase 1 ( SGK1 )
Boulbes et al., Mol Cancer Res 2010 (Cell Transformation, Neoplastic) : Rictor phosphorylation on the Thr-1135 site does not require mammalian target of rapamycin complex 2
Chen et al., Mol Carcinog 2010 (Neoplasms) : In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin mediated phosphorylation of Akt and ERK , and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin based therapeutic approaches in cancer cells ... Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin based therapeutic approaches in cancer cells
Cleveland-Donovan et al., Endocrinology 2010 (Obesity) : The mammalian target of rapamycin (mTOR)-Rictor complex regulates phosphorylation of AKT-serine ( 473 ) in 3T3-L1 adipocytes, but knockdown of Rictor by lentivirus delivered short hairpin RNA in sc preadipocytes did not affect AKT-serine ( 473 ) phosphorylation by IGF-I
Lee et al., Immunity 2010 : mTORC2 promoted phosphorylation of protein kinase B ( PKB, or Akt ) and PKC, Akt activity, and nuclear NF-kappaB transcription factors in response to T cell activation
Kim et al., J Lipid Res 2010 : GIP induced phospho-CREB and TORC2 were shown to bind to a cAMP-response element ( -II ) site in the human LPL promoter and GIP increased protein-protein interactions of these two factors ... The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation ... The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation ... The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation
Lazorchak et al., Mol Cell 2010 : We further show that Akt2 specifically mediates the Sin1-mTORC2 dependent suppression of il7r and rag gene expression in B cells by regulating FoxO1 phosphorylation
Mansley et al., Br J Pharmacol 2010 : TORC2 , but not TORC1, is also involved in glucocorticoid induced SGK1 activation but its role is permissive
Vu et al., Clin Cancer Res 2010 (Leukemia...) : The majority of preclinical and clinical efforts to target TOR have involved using rapamycin and its analogs ( rapalogs ), which suppress TORC1 only partially and do not acutely inhibit TORC2
Lee et al., Genes Dev 2010 : Collectively, these findings establish mTOR/rictor mediated Akt activation as a key driver of NSC proliferation and gliogenesis, and identify a unique mechanism for conferring brain region-specific responses to cancer causing genetic changes
Phu et al., Cell Signal 2011 : Overexpressed DLK induced the phosphorylation of TORC2 and TORC1 on Ser-171 and 167, respectively and on additional residues
Kuehn et al., J Biol Chem 2011 : In mouse bone marrow derived mast cells, PGE ( 2 ) was found to induce activation of mTORC1 ( mTOR complexed to raptor ) as indicated by increased p70S6K and 4E-BP1 phosphorylation, and activation of mTORC2 ( mTOR complexed to rictor ), as indicated by increased phosphorylation of AKT at position Ser ( 473 ) ... In mouse bone marrow derived mast cells, PGE ( 2 ) was found to induce activation of mTORC1 ( mTOR complexed to raptor ) as indicated by increased p70S6K and 4E-BP1 phosphorylation, and activation of mTORC2 ( mTOR complexed to rictor ), as indicated by increased phosphorylation of AKT at position Ser ( 473 )
Tatebe et al., Curr Biol 2010 : Human Rab6 can substitute Ryh1 in S. pombe, and therefore Rab6 may be a potential activator of TORC2 in mammals
Liu et al., J Neuroendocrinol 2011 : The demonstration that TORC2 translocates to the nucleus of hypothalamic CRH neurones and interacts with the CRH promoter in conjunction with the activation of CRH transcription during restraint stress, provides strong evidence for the involvement of TORC2 in the physiological regulation of CRH transcription
Dunaway et al., Mol Cell Biol 2011 : Slit2 stimulates angiogenesis through mTORC2 dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1 ... Slit2 stimulates angiogenesis through mTORC2 dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1
Murata et al., J Biol Chem 2011 (Neuroblastoma...) : A new cytosolic pathway from a Parkinson disease associated kinase, BRPK/PINK1 : activation of AKT via mTORC2
Shen et al., International journal of clinical and experimental pathology 2010 (Carcinoma, Endometrioid...) : mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt
Chong et al., Oxidative medicine and cellular longevity 2010 (Neurodegenerative Diseases) : The function of mTOR signaling is mediated primarily through two mTOR complexes : mTORC1 and mTORC2
Harston et al., Am J Physiol Heart Circ Physiol 2011 (Hypertrophy) : Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes : mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival ... Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes : mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival
Pearce et al., Biochem J 2011 : Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members : mTORC1 phosphorylates S6K ( S6 kinase ), whereas mTORC2 regulates phosphorylation of Akt, PKCa ( protein kinase Ca ) and SGK1 ( serum- and glucocorticoid induced protein kinase 1 ) ... Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members : mTORC1 phosphorylates S6K ( S6 kinase ), whereas mTORC2 regulates phosphorylation of Akt , PKCa ( protein kinase Ca ) and SGK1 ( serum- and glucocorticoid induced protein kinase 1 ) ... Taken together, these results suggest that Protor-1 may play a role in enabling mTORC2 to efficiently activate SGK1 , at least in the kidney
Guo et al., Arterioscler Thromb Vasc Biol 2011 : According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity ... According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation , which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity
Gulhati et al., Cancer Res 2011 (Colorectal Neoplasms...) : mTORC1 and mTORC2 regulate EMT , motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways
Saci et al., Mol Cell 2011 : Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size
Goncharova et al., Mol Cell Biol 2011 : Our data demonstrate that mTORC2 dependent activation of RhoA is required for TSC2-null cell growth and survival and suggest that targeting both mTORC2 and mTORC1 by a combination of proapoptotic simvastatin and cytostatic rapamycin shows promise for combinational therapeutic intervention in diseases with TSC2 dysfunction
Jaafar et al., J Biol Chem 2011 : Vasopressin stimulation also induced phosphorylation of Akt on Ser-473 through PLD1 dependent activation of mTORC2 complex
Hiraoka et al., Oncogene 2011 : A well conserved threonine in the turn motif ( TM ) is also constitutively phosphorylated by mTORC2 and contributes to the stability of Akt
Moore et al., J Biol Chem 2011 (MAP Kinase Signaling System) : In this study, we investigated the role of the mammalian target of rapamycin complex ( mTORC)-2 in Akt regulation using the recently identified small molecule ATP competitive mTOR inhibitors PP242 and Torin1
Joha et al., Oncogene 2012 (Leukemia, Myelogenous, Chronic, BCR-ABL Positive) : Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL ( + ) cells and indicate that regulation by GILZ may influence TKI sensitivity ... Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL ( + ) cells and indicate that regulation by GILZ may influence TKI sensitivity
O'Brien et al., Eur J Immunol 2011 : Overall, our results demonstrate that TSC1 differentially regulates mTORC1 and mTORC2 activity, promotes T-cell survival, and is critical for normal mitochondrial homeostasis in T cells
Lazorchak et al., Protein & cell 2011 (Cell Transformation, Neoplastic) : We also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability
Boulbés et al., Biochem Biophys Res Commun 2011 : Based on our study we suggest that the mTORC2 dependent phosphorylation of Akt on Ser-473 takes place on the surface of ER
Hwang et al., BMB Rep 2011 (Ischemia) : The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2 , which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt
Chen et al., J Biol Chem 2011 : The PI3K dependent signaling kinase complex mTORC2 ( mammalian target of rapamycin complex 2 ) has been defined as the regulatory Ser-473 kinase of Akt
Zhao et al., Mol Cell 2011 : DEPTOR , an inhibitor of mTORC1 and mTORC2 , is degraded via ubiquitin-proteasome pathway by an unknown E3 ubiquitin ligase
Gupta et al., Blood 2012 (Lymphoma) : Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies
Glidden et al., J Biol Chem 2012 : Although Rictor is required for the stability and activity of mTORC2 , little is known about functional regions or post-translational modifications within Rictor that are responsible for regulating mTORC2 ... p300 mediated acetylation of Rictor increases mTORC2 activity toward Akt, whereas site directed mutants within the acetylation region of Rictor exhibit reduced insulin-like growth factor 1 (IGF-1) stimulated mTORC2 kinase activity
Liu et al., Endocrinology 2012 : Overexpression of either SIK1 or SIK2 in 4B cells reduced nuclear TORC2 levels ( Western blot ) and inhibited forskolin stimulated CRH transcription ( luciferase assay )
Koh et al., Endocr Relat Cancer 2012 (Carcinoma...) : Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex dependent and TORC2 complex independent mechanisms respectively ... Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex dependent and TORC2 complex independent mechanisms respectively
Shu et al., Mol Biol Cell 2012 : Synthesis of cAMP receptor and adenylyl cyclase A ( ACA ) is inhibited, and activation of ACA, RasC, and RasG, phosphorylation of extracellular signal regulated kinase 2 , activation of TORC2 , and stimulation of actin polymerization and myosin assembly are greatly reduced ... Synthesis of cAMP receptor and adenylyl cyclase A ( ACA ) is inhibited, and activation of ACA, RasC, and RasG, phosphorylation of extracellular signal regulated kinase 2, activation of TORC2 , and stimulation of actin polymerization and myosin assembly are greatly reduced
Fang et al., J Biol Chem 2012 (Prostatic Neoplasms) : Significantly, androgen increased TORC2 mediated AKT S473 phosphorylation without affecting the PDK1 mediated AKT T308 phosphorylation or TORC1 activity ... This study reveals a pathway linking AR to a selective activation of TORC2 , the subsequent activation of AKT , and phosphorylation of a discrete set of AKT substrates that regulate cellular proliferation and survival
Rodrik-Outmezguine et al., Cancer Discov 2011 : mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin ... mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin ... Inhibition of mTORC2 leads to AKT serine 473 ( S473 ) dephosphorylation and a rapid but transient inhibition of AKT T308 phosphorylation and AKT signaling
Espona-Fiedler et al., Biochem Pharmacol 2012 (Melanoma) : The inhibition of mTORC1 and mTORC2 complexes by PG or OBX resulted in a loss of AKT phosphorylation at S473, preventing its full activation, with no significant effect on T308
Misra et al., J Cell Biochem 2012 (Prostatic Neoplasms) : We measured mTORC2 dependent Akt phosphorylation at S473 in immunoprecipitates of mTOR or Rictor from 1-LN cells ... These studies represent the first report that Epac1 mediates mTORC2 dependent phosphorylation of Akt ( S473 ) ... We further demonstrate that in 8-CPT-2Me-cAMP treated cells, Epac1 co-immunoprecipitates with AKAP, Raptor, Rictor, PDE3B, and PDE4D suggesting thereby that during Epac1 induced activation of mTORC1 and mTORC2 , Epac1 may have an additional function as a `` scaffold '' protein
Mazei-Robison et al., Neuron 2011 : Chronic morphine decreases mTORC2 activity, and overexpression of Rictor , a component of mTORC2, prevents morphine induced changes in cell morphology and activity
Rosel et al., J Cell Sci 2012 : TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state ; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization
Pracheil et al., Genetics 2012 : More importantly, characterization of lst8d bypass mutants reveals a role for protein phosphatase 2A (PP2A) in the regulation of TORC2 signaling
Zhang et al., Proc Natl Acad Sci U S A 2012 : Taken together, these data reveal a signaling pathway by which phosphatidic acid synthesized via the glycerol-3-phosphate pathway inhibits mTORC2 activity by decreasing the association of rictor and mTOR , thereby down regulating insulin action
Rao et al., Immunity 2012 : The Foxo1 inactivation was dependent on mTORC1 kinase, given that blockade of mTORC1 abrogated mTORC2 mediated Akt ( Ser473 ) kinase phosphorylation, resulting in Foxo1 dependent switch from T-bet to Eomesodermin transcription factor activation and increase in memory precursors ... The Foxo1 inactivation was dependent on mTORC1 kinase, given that blockade of mTORC1 abrogated mTORC2 mediated Akt ( Ser473 ) kinase phosphorylation, resulting in Foxo1 dependent switch from T-bet to Eomesodermin transcription factor activation and increase in memory precursors
Wahdan-Alaswad et al., Mol Cancer Res 2012 (Prostatic Neoplasms) : Intriguingly, silencing raptor alone enhanced, whereas silencing rictor repressed, the phosphorylation of Smad1/5, indicating that mTORC1 represses, whereas mTORC2 activates , BMP signaling
Lamming et al., Science 2012 (Insulin Resistance) : We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin mediated suppression of hepatic gluconeogenesis
Wang et al., Mol Cell Biol 2012 (Dermatitis, Seborrheic) : Surprisingly, however, TORC2 does not regulate cell growth via its best characterized target, AKT
Kaur et al., Proc Natl Acad Sci U S A 2012 : We provide evidence that mTORC2 complexes control IFN induced phosphorylation of AKT on serine 473 and their function is ultimately required for IFN dependent gene transcription via interferon stimulated response elements
Chang et al., Eur J Immunol 2012 : Sin1 deficiency blocks the mTORC2 dependent Akt phosphorylation in T cells during development and activation
Shanmugasundaram et al., Oncogene 2013 (Carcinoma, Renal Cell...) : Here we provide additional genetic evidence that PI3K signaling activates mTORC2 kinase activity ... We also demonstrate a novel role for mTORC2 in the modulation of nuclear p27 levels
Zhao et al., Neoplasia (New York, N.Y.) 2012 (Neoplasms) : Recently, we and others found that DEPTOR , a naturally occurring inhibitor of both mTORC1 and mTORC2 , was degraded by SCF ( Skp1-Cullin-F box proteins ) E3 ubiquitin ligase, the founding member of cullin-RING-ligases ( CRLs ), resulting in mTOR activation and cell proliferation
Agarwal et al., Oncogene 2013 : We found that a suppression of RhoGDI2 by rictor is not related to the Sin1 or raptor function that excludes a role of mTORC2 or mTORC1 in regulation of RhoGDI2
Floc'h et al., Cancer Res 2012 (Disease Models, Animal...) : In human prostate cancer cell lines, although not in the mouse model, the synergistic actions of MK-2206 and ridaforolimus ( MK-8669 ) are due in part to limiting the mTORC2 feedback activation of Akt
Wang et al., Biochem Biophys Res Commun 2012 (Vitreoretinopathy, Proliferative) : In conclusion, this study suggest that TNF-a promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling
Hall et al., Breast Cancer Res Treat 2012 (Breast Neoplasms) : Previous studies have alternatively suggested that either mTORC1 or mTORC2 is exclusively required for SGK1 's Ser422 phosphorylation and activation in breast cancer cells
Magee et al., Cell stem cell 2012 (Leukemia) : Pten is therefore required in adult, but not neonatal, HSCs to negatively regulate mTORC2 signaling
Ju et al., Cell Signal 2013 : We have previously demonstrated that syndecan 4 (S4) regulates the intracellular localization of mTORC2 , thus altering phosphorylation of Akt at serine473 ( Ser473 ), one of two critical phosphorylation sites essential for the full activation of Akt [1 ]
Chong et al., Prog Neurobiol 2012 (Neurodegenerative Diseases) : mTOR signaling is dependent upon the mTORC1 and mTORC2 complexes that are composed of mTOR and several regulatory proteins including the tuberous sclerosis complex ( TSC1, hamartin/TSC2, tuberin )
Najafov et al., Biochem J 2012 (Neoplasms) : Akt is activated by phosphorylation of its T-loop residue ( Thr ( 308 ) ) by PDK1 ( 3-phosphoinositide dependent kinase-1 ) and its C-terminal hydrophobic motif ( Ser ( 473 ) ) by mTORC2 [ mTOR ( mammalian target of rapamycin ) complex 2 ] ... Akt is activated by phosphorylation of its T-loop residue ( Thr ( 308 ) ) by PDK1 ( 3-phosphoinositide dependent kinase-1 ) and its C-terminal hydrophobic motif ( Ser ( 473 ) ) by mTORC2 [ mTOR ( mammalian target of rapamycin ) complex 2 ]
Le Bacquer et al., J Endocrinol 2013 (Hyperglycemia) : mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells
Ethier et al., PloS one 2012 (Necrosis) : In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate
Matheny et al., Growth Factors 2012 : Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110ß-deficient myoblasts is mediated by PI3K p110a and mTORC2
Kim et al., Mol Cell 2012 : Here, we found that mTORC2 can also regulate insulin signaling at the level of insulin receptor substrate-1 (IRS-1) ... Our findings reveal that in addition to persistent mTORC1 signaling, heightened mTORC2 signals can promote insulin resistance due to mTORC2 mediated degradation of IRS-1
Maru et al., J Urol 2013 (Carcinoma, Renal Cell...) : We investigated whether mTORC2 regulates E-cadherin expression and controls cell motility during HIF-2a down-regulation in renal cell carcinoma cells ... Results show that mTORC2 might regulate E-cadherin expression and suppress cell motility by controlling the mTORC2-HIF-2a signaling pathway
Chen et al., J Invest Dermatol 2013 (Psoriasis) : mTORC2-PKBa/Akt1 Serine 473 Phosphorylation Axis Is Essential for Regulation of FOXP3 Stability by Chemokine CCL3 in Psoriasis
Parrales et al., Cell Signal 2013 : Since Akt functions as an upstream activator of mechanistic target of rapamycin complex 1 ( mTORC1 ) and is also a downstream target for mTORC2 , the aim of this work was to determine whether mTOR is involved in thrombin induced RPE cell proliferation by regulating cyclin D1 expression in immortalized rat RPE-J cell line
Yao et al., Science signaling 2013 : BSTA promotes mTORC2 mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation ... The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation ... The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation
Razmara et al., Cell communication and signaling : CCS 2013 : Inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited PDGF-BB activation of both mTORC1 and mTORC2 ... Inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited PDGF-BB activation of both mTORC1 and mTORC2 ... Thus, whereas both mTORC1 and mTORC2 are activated in a PI3K dependent manner, different additional signaling pathways are needed ... mTORC1 is activated in a PLD dependent manner and promotes phosphorylation of the S6 protein, whereas mTORC2 , in concert with PLC? signaling, promotes Akt phosphorylation
Shortt et al., Blood 2013 (Lymphoma, B-Cell) : Moreover, apoptosis was initiated at drug concentrations insufficient to antagonize PI3K/mTORC2 regulated AKT phosphorylation
Wolin et al., Cancer Lett 2013 (Neuroendocrine Tumors...) : The mTOR inhibitor everolimus has been approved by the FDA for the treatment of pNET, but its efficacy may be limited by its inability to prevent mTORC2 mediated activation of Akt
Esen et al., Cell Metab 2013 : Deletion of Lrp5 in the mouse, which decreases postnatal bone mass, reduces mTORC2 activity and glycolytic enzymes in bone cells and lowers serum lactate levels
Pracheil et al., J Biol Chem 2013 : It has been reported that protein phosphatase 2A (PP2A) and the Far3-7-8-9-10-11 complex ( Far complex ) negatively regulate TORC2 signaling in yeast
Moschella et al., Cell Signal 2013 : Since mTORC2 is known to mediate the activation of a prosurvival kinase, Akt, we analyzed whether mTORC2 directly mediates Akt activation or whether it requires the participation of another prosurvival kinase, PKCe ( epsilon isoform of protein kinase-C )
Jeon et al., Biochim Biophys Acta 2013 (Breast Neoplasms...) : When SelW was down-regulated, mTORC2 dependent phosphorylation of Akt at Ser473 was decreased
Pan et al., J Immunol 2013 : Its deficiency in DCs results in increased mammalian target of rapamycin (mTOR) complex 1 but decreased mTORC2 signaling, altered cytokine production, impaired CIITA/MHC-II expression, and defective Ag presentation to CD4 T cells after TLR4 stimulation
Melnik et al., Exp Dermatol 2013 : Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling ... Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling
Völkers et al., Proc Natl Acad Sci U S A 2013 (Cardiomegaly) : Inhibition of mTORC1 by PRAS40 preferentially promotes protective mTORC2 signaling in chronic diseased myocardium
Jaafar et al., Cell communication and signaling : CCS 2013 (Muscular Atrophy) : These observations suggest that PLD1 acts through the activation of both mTORC1 and mTORC2 to induce positive trophic effects on muscle cells
Wang et al., PloS one 2013 : Western blotting showed that the PP242 inhibition of mTORC2 mediated AKT phosphorylation at Ser 473 ( AKT ( S473 ) ) was transient only in the first few hours of the PP242 treatment ... The parallel increase of AKT ( S473 ) and EGFR ( T1068 ) in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2