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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining

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MTOR — TSC2

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Lu et al., Blood 2013 (Multiple Myeloma) : We identify TSC2 , a negative regulator of mTOR-C1 , as a novel Pim2 substrate and show that Pim2 directly phosphorylates TSC2 on Ser-1798 and relieves the suppression of TSC2 on mTOR-C1
Balgi et al., PloS one 2009 : TSC2 , a negative regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone ... Transient exposure of immortalized mouse embryo fibroblasts to these drugs was not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in starvation conditions, by a mechanism determined in large part by the tuberous sclerosis complex protein TSC2 , an upstream regulator of mTORC1
Weichhart et al., Immunity 2008 (Inflammation...) : Conversely, deletion of TSC2 , the key negative regulator of mTOR , diminished NF-kappaB but enhanced STAT3 activity and reversed this proinflammatory cytokine shift
Kaur et al., J Biol Chem 2007 : Interestingly, the induction of expression of ISG15 and CXCL10 proteins by IFNs was also strongly enhanced in cells lacking expression of the tuberin ( TSC2 ( -/- ) ) or hamartin ( TSC1 ( -/- ) ) genes, consistent with the known negative regulatory effect of the TSC1-TSC2 complex on mTOR activation
Tee et al., Semin Cell Dev Biol 2005 (Disease...) : Recent studies reveal that the tuberous sclerosis complex (TSC)-1/2 , PTEN, and LKB1 tumor suppressor proteins tightly control mTOR
Wang et al., Biochim Biophys Acta 2013 (Genetic Diseases, X-Linked...) : By promoting TSC2 degradation, CUL4B could positively regulate mTOR activity in neocortical neurons of frontal cortex ... Consistent with this hypothesis, CUL4B knockdown induced upregulation of TSC2 in neocortical neurons resulted in a decreased protein level of active phospho-mTOR ( Ser2448 ) and a reduced expression of active phospho-p70S6K ( Thr389 ) and phospho-4E-BP1 ( Thr37/46 ), two main substrates of mTOR mediated phosphorylation
Vary et al., J Nutr 2006 : Likewise, the extent of phosphorylation of TSC2 , a potential upstream regulator of mTOR , was not significantly altered during meal feeding
O'Brien et al., Arch Immunol Ther Exp (Warsz) 2012 (MAP Kinase Signaling System) : Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling
Wang et al., Autophagy 2012 (Brain Ischemia...) : Overexpression or knockdown of Nampt regulated the phosphorylation of mTOR and S6K1 signaling pathway upon OGD stress through enhancing phosphorylation of TSC2 at Ser1387 but not Thr1462 site
Lee et al., EMBO J 2007 (Hamartoma...) : Thus, loss of TSC1 or TSC2 , the negative regulators of mTOR , results in dramatic accumulation of p53 and apoptosis in response to stress conditions
Sarkar et al., Mol Cell 2011 (Huntington Disease) : Additionally, NO inhibits IKKß and reduces AMPK phosphorylation, leading to mTORC1 activation via TSC2
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
Buller et al., Am J Physiol Cell Physiol 2008 : Since GSK-3 can inhibit mammalian target of rapamycin (mTOR) signaling via phosphorylation of the tuberous sclerosis complex subunit 2 ( TSC2 ) tumor suppressor, we investigated whether chronic GSK-3 effects on glucose uptake and GLUT1 expression depended on TSC2 phosphorylation and TSC inhibition of mTOR
Huang et al., Mol Cell Biol 2008 : The TSC1-TSC2 complex is required for proper activation of mTOR complex 2 ... 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 ... These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2 , which through different mechanisms promotes Akt activation
Ru et al., J Mol Neurosci 2012 : A role of the mammalian target of rapamycin (mTOR) in glutamate induced down-regulation of tuberous sclerosis complex proteins 2 ( TSC2 ) ... Interestingly, the mTOR-specific inhibitor rapamycin blocks the glutamate induced TSC2 down-regulation ... This finding suggests that NMDAR activation evokes an mTOR mediated negative regulation of TSC2
Vega-Rubin-de-Celis et al., Biochemistry 2010 : REDD1 induced-mTORC1 inhibition requires the TSC1/TSC2 complex , and REDD1 has been proposed to act by directly binding to and sequestering 14-3-3 proteins away from TSC2 leading to TSC2 dependent inhibition of mTORC1 ... REDD1 induced-mTORC1 inhibition requires the TSC1/TSC2 complex, and REDD1 has been proposed to act by directly binding to and sequestering 14-3-3 proteins away from TSC2 leading to TSC2 dependent inhibition of mTORC1
Nie et al., Nat Neurosci 2010 : Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin induced growth cone collapse
Alexander et al., Cell cycle (Georgetown, Tex.) 2010 : We found that TSC2 activation results in mTORC1 repression and subsequent induction of autophagy
Tanwar et al., PLoS Genet 2012 (Adenoma...) : Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2 , regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1 deleted stroma contributes to the phenotype
Yu et al., Mol Cancer Ther 2008 : Overexpression of constitutively activated Akt or disruption of TSC1-TSC2 complex by small interfering RNA or gene knockout only partially restored curcumin mediated inhibition of mTOR and downstream signaling, indicating that they are not the primary effectors of curcumin mediated inhibition of Akt/mTOR signaling
Habib et al., Genes & cancer 2011 : These novel data provide evidence that loss of TSC-2 , PTEN, and p53 as well as activation of PI 3-K and mTOR is associated with kidney cancer in the Eker rat, while sustained expression of TSC-2, PTEN, and p53 may prevent progression of kidney cancer in TSC patients
Arvisais et al., J Biol Chem 2006 : AKT independent phosphorylation of TSC2 and activation of mTOR and ribosomal protein S6 kinase signaling by prostaglandin F2alpha
Liu et al., J Biol Chem 2011 (Colonic Neoplasms) : In contrast, stable knockdown of TSC2 , a negative regulator of mTOR activity, increases PHLPP expression
Kato et al., PloS one 2013 : Knockdown of TSC2 , a negative regulator of mTORC1 , caused activation of mTORC1 and enhanced Cd induction of the IRE1-JNK pathway and apoptosis without affecting other UPR branches
Weichhart et al., Blood 2011 : Interestingly, long-term activation of monocytes with lipopolysaccharide enhanced the expression of TSC2 , the principle negative regulator of mTOR, whereas dexamethasone blocked TSC2 expression and reestablished mTOR activation
Koyanagi et al., PloS one 2011 : Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells
Zhang et al., Breast Cancer Res Treat 2012 (Breast Neoplasms) : Although NDGA stimulated AMP activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) signaling, which negatively regulates mTORC1, AMPK and TSC2 deletion could not diminish the inhibition of mTORC1 by NDGA
Gan et al., J Biol Chem 2006 : Together, these results suggest that FAK might regulate S6K activation and cell size through its interaction with and phosphorylation of TSC2 and also provide a previously unappreciated role of TSC2 in the regulation of mTOR signaling by cell adhesion
Sun et al., Proc Natl Acad Sci U S A 2011 (Neoplasms) : PKM2 level was augmented in mouse kidney tumors due to deficiency of tuberous sclerosis complex 2 and consequent mTOR activation , and was reduced in human cancer cells by mTOR suppression
Melnik et al., Exp Dermatol 2013 : Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling
DeYoung et al., Genes Dev 2008 (Breast Neoplasms) : REDD1 mutants that fail to bind 14-3-3 are defective in eliciting TSC2/14-3-3 dissociation and mTORC1 inhibition , while TSC2 mutants that do not bind 14-3-3 are inactive in hypoxia signaling to mTORC1
Brugarolas et al., Genes Dev 2004 (Anoxia) : Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801
Pollizzi et al., Molecular cancer 2009 (Disease Models, Animal...) : Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 and suppression of AKT
Hayashi et al., Am J Physiol Endocrinol Metab 2007 : Consistent with this, GH increased the phosphorylation of TSC2 , an upstream regulator of mTORC1 , at sites that are targets for Akt/PKB
Korotchkina et al., Aging 2010 : Here we showed that shRNA mediated knockdown of TSC2 , a negative regulator of mTOR , partially converted quiescence into senescence in these nutlin arrested cells
Paturi et al., J Appl Physiol 2010 (Cumulative Trauma Disorders...) : The amount of Tuberin/TSC2 phosphorylation, an inhibitor of mTOR , was unchanged in the LZ soleus after overload while it was increased ( 68.3 %, P < 0.05 ) in OZ animals
Das et al., J Biol Chem 2012 (Tuberous Sclerosis) : TSC2 deficiency induces constitutive activation of mTOR , leading to a state of insulin resistance due to a negative feedback regulation, resulting in reduced Akt phosphorylation
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 ... In examining the requirements for different Akt mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis
Goncharova et al., Mol Pharmacol 2008 (Leiomyoma...) : Our study demonstrates that IFNbeta dependent activation of STATs and p38 MAPK is not sufficient to fully inhibit proliferation of cells with TSC2 dysfunction and that TSC2 dependent inhibition of mTOR/S6K1 cooperates with IFNbeta in inhibiting human LAM and TSC2-null ELT3 cell proliferation
Wolff et al., Mol Cell Biol 2011 (Anoxia) : We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex
Mills et al., Proc Natl Acad Sci U S A 2008 (Lymphoma) : Here, we demonstrate that loss of TSC2 in the E mu-myc murine lymphoma model leads to mTORC1 activation and accelerated oncogenesis caused by a defective apoptotic program despite compromised AKT phosphorylation
Linehan et al., Nat Rev Urol 2010 (Carcinoma, Renal Cell...) : TSC1-TSC2 is downstream of AMPK and negatively regulates mTOR in response to cellular energy deficit
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
Jozwiak et al., J Neurooncol 2006 (Brain Neoplasms...) : The importance of these proteins is confirmed by their ubiquitous character and by the fact that TSC1/TSC2 complex is involved in the regulation of the activity of mTOR , a master controller of protein translation
Lu et al., Clin Cancer Res 2008 (Endometrial Neoplasms...) : Loss of tuberous sclerosis complex-2 function and activation of mammalian target of rapamycin signaling in endometrial carcinoma ... In tumors that retained TSC2 expression, phosphorylation of tuberin at S939 was observed with a high frequency, indicating that mTOR repression by TSC2 had been relieved via AKT phosphorylation of this tumor suppressor
Sofer et al., Mol Cell Biol 2005 : REDD1 likely acts on the TSC1/2 complex, as regulation of mTOR substrate phosphorylation by REDD1 requires TSC2 and is blocked by overexpression of the TSC1/2 downstream target Rheb but is not blocked by inhibition of AMPK
Smith et al., J Biol Chem 2005 : The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses ... Some studies have suggested that TSC2 also mediates the control of mTOR by amino acids ... Although TSC2 is not required for amino acid control of mTOR , amino acid withdrawal does decrease the proportion of Rheb in the active GTP bound state
Coevoets et al., Eur J Hum Genet 2009 (Tuberous Sclerosis) : We have developed a straightforward, semiautomated in-cell western ( ICW ) assay to investigate the effects of amino acid changes on the TSC1-TSC2 dependent inhibition of mTOR activity
Inoki et al., Genes Dev 2003 : These functions of TSC1/TSC2 are likely mediated by mTOR
Mak et al., Cancer Invest 2004 (Tuberous Sclerosis) : Tuberin , serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival
Qi et al., Eur J Pharmacol 2013 : Activation of mTOR by insulin or inhibition of endogenous TSC2 levels by siRNA obviously delayed PAB induced senescence
Sviripa et al., Bioorg Med Chem Lett 2013 : AMPK also regulates lipid synthesis by inhibiting acetyl-CoA carboxylase (ACC) and regulates mTOR signaling by activating TSC2
Rolfe et al., Biochem J 2005 : PE stimulation of cardiomyocytes induced the phosphorylation of TSC2 ( tuberous sclerosis complex 2 ), a negative regulator of mTOR activity
Lacher et al., Oncogene 2010 (Cell Transformation, Neoplastic...) : TSC2 negatively regulates the activity of the GTPase Rheb and thereby inhibits mammalian target of rapamycin complex 1 ( mTORC1 ) signaling
Dey et al., PloS one 2012 (Hypertrophy) : Tuberin and PRAS40, two other Akt substrates, and endogenous inhibitors of mTORC1 , regulate mesangial cell hypertrophy
Inoki et al., Nat Cell Biol 2002 (Tuberous Sclerosis) : These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR)
Henske , Pediatr Nephrol 2005 (Angiomyolipoma...) : Recently, the TSC1/TSC2 protein complex was shown to inhibit the kinase mTOR ( mammalian target of rapamycin )
Hong-Brown et al., Am J Physiol Cell Physiol 2012 : Rag GTPases and AMPK/TSC2/Rheb mediate the differential regulation of mTORC1 signaling in response to alcohol and leucine
O'Brien et al., Eur J Immunol 2011 : The TSC1/TSC2 complex has been shown to inhibit mTORC1 signaling in cell line models
Yoshida et al., Nat Med 2010 (Pulmonary Emphysema) : Rtp801 ( also known as Redd1, and encoded by Ddit4 ), a stress related protein triggered by adverse environmental conditions, inhibits mammalian target of rapamycin (mTOR) by stabilizing the TSC1-TSC2 inhibitory complex and enhances oxidative stress dependent cell death
Hahn-Windgassen et al., J Biol Chem 2005 : Our results demonstrate that Akt lies upstream of these two pathways and induces full inhibition of TSC2 and activation of mTOR both through direct phosphorylation and by inhibition of AMPK mediated phosphorylation of TSC2
Guo et al., Mol Cancer Res 2013 : Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1
Cook et al., Cancer Res 2012 : Mechanistically, GRP78 integrated multiple cellular signaling pathways to inhibit apoptosis and stimulate prosurvival autophagy, which was dependent on TSC2/AMPK mediated mTOR inhibition but not on beclin-1
Shaw et al., Cancer Cell 2004 (Colonic Polyps...) : Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2 dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR
Tzatsos et al., J Biol Chem 2007 : Energy depletion activates AMP activated protein kinase (AMPK) and inhibits cell growth via TSC2 dependent suppression of mTORC1 signaling
Mak et al., Am J Pathol 2005 (Angiomyolipoma...) : Besides the negative regulatory role of the TSC1/TSC2 proteins on mTOR , we have reported an effect on beta-catenin signaling at the level of the degradation complex in vitro