Gene interactions and pathways from curated databases and text-mining

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Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Sarbassov et al., Mol Cell 2006 : mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival
Guertin et al., Dev Cell 2006 : mLST8 is necessary to maintain the rictor-mTOR, but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKCalpha, but not S6K1
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
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
Masri et al., Cancer Res 2007 (Brain Neoplasms...) : mTORC2 has recently been shown to phosphorylate and activate Akt
Wang et al., Cancer Res 2008 (Lung Neoplasms) : Collectively, we conclude that inhibition of the mTOR/raptor complex initiates Akt activation independent of mTOR/rictor
Hietakangas et al., BMC cancer 2008 (Breast Neoplasms...) : TOR complex 2 (TORC2) activates AKT by phosphorylating it on the ` hydrophobic motif ' site
Bentzinger et al., Cell Metab 2008 (Muscular Dystrophies) : Finally, we show that activation of PKB/Akt does not require mTORC2
Brito et al., Atherosclerosis 2009 (Atherosclerosis) : The activation of mTOR signaling by oxLDL, requires the upstream activation of PI3K and Akt , as assessed by the inhibitory effect of the PI3K inhibitor Ly294002 on mTOR activation and DNA synthesis
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
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
Breuleux et al., Mol Cancer Ther 2009 (Neoplasms) : Strikingly, rictor down-regulation attenuated AKT S473 phosphorylation induced by mTORC1 inhibition
Pollizzi et al., Molecular cancer 2009 (Disease Models, Animal...) : Recent studies indicate that inhibition of mTORC1 with RAD001 ( everolimus ) leads to rebound activation of AKT , which could protect tumors from drug induced cell death
Tzatsos et al., J Biol Chem 2009 : Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold dependent
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
Park et al., Haematologica 2010 (Leukemia, Myeloid, Acute) : However, as mTORC1 activation is independent of PI3K/AKT in acute myeloid leukemia, dual PI3K and mTOR inhibitors may induce apoptosis in blast cells
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 ... Interestingly, mTORC1 negatively regulates Akt activation, but whether mTORC1 signaling directly targets mTORC2 remains unknown ... However, cells expressing a Rictor T1135A mutant were found to have increased mTORC2 dependent phosphorylation of Akt
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
Lee et al., Carcinogenesis 2010 (Colonic Neoplasms) : In contrast, the Akt dependent mTORC1 inhibition by selenium did not require AMPKalpha ( 1 )
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
Wu et al., Urol Oncol 2012 (Carcinoma, Transitional Cell...) : The present findings also suggest rictor dependent AKT activation as a consequence of mTORC1 inhibition
Sini et al., Autophagy 2010 (Neoplasms) : mTORC2 activates AKT directly by phosphorylating Serine 473
Timmerman et al., J Clin Endocrinol Metab 2010 : During insulin infusion, blood flow and capillary recruitment increased in the control ( P < 0.05 ) group only ; Akt phosphorylation and glucose uptake increased in both groups ( P < 0.05 ), with no group differences ; and mTORC1 signaling increased more in control ( P < 0.05 ) than in L-NMMA
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
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., 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
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
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
Lee et al., PloS one 2010 (Endotoxemia) : Furthermore, in vitro cellular studies demonstrated that LPS ( lipopolysaccharide ) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways
Winter et al., Am J Physiol Cell Physiol 2011 : Previous studies have shown that, in part, Akt and ERK promote mTORC1 signaling through phosphorylation of a GTPase activator protein (GAP), referred to as tuberous sclerosis complex 2 (TSC2), that acts as an upstream inhibitor of mTORC1
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
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 )
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
Wenner et al., J Cell Physiol 2012 (Neoplasms) : In addition, chemotherapeutic approaches based on Akt activated mTORC1 are described, and their relationship to the role of aerobic glycolysis in this protection
Tanaka et al., Clin Cancer Res 2011 (Neoplasms) : Effects on Akt phosphorylation induced by mTORC1 inhibition were tested with CH5132799 and compared with mTORC1 and PI3K/mTOR inhibitors
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
Kato et al., Cell Death Differ 2012 (MAP Kinase Signaling System) : Activation of mTORC1 reduced Akt phosphorylation, which was an event upstream of IRE-JNK signaling and consequent apoptosis ... These results disclosed that, under ER stress conditions, mTORC1 causes apoptosis through suppression of Akt and consequent induction of the IRE1-JNK pathway
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
Magri et al., Cell stem cell 2011 (Epilepsy...) : Notably, mTORC1 dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs
Gupta et al., Blood 2012 (Lymphoma) : Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies ... Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies
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
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 ... Inhibition of mTORC2 leads to AKT serine 473 ( S473 ) dephosphorylation and a rapid but transient inhibition of AKT T308 phosphorylation and AKT signaling
Willems et al., Leukemia 2012 (Leukemia, Myeloid, Acute) : In addition, the mTORC1 dependent PI3K/Akt feedback activation was fully abrogated in AZD8055 treated AML cells
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 ... 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 )
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
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
Gulhati et al., Carcinogenesis 2012 (Colorectal Neoplasms...) : In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance
Nölting et al., J Mol Endocrinol 2012 : Lovastatin alone significantly reduced MPC and MTT cell viability at therapeutically relevant doses and inhibited both ERK and AKT signalling, but increased mTORC1/p70S6K signalling
Urbanska et al., J Biol Chem 2012 : We also identified Akt as a downstream effector of mTORC2 needed for proper dendritic arbor morphology, the action of which required mTORC1 and p70S6K1
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
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 ]
Matheny et al., Growth Factors 2012 : Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110ß-deficient myoblasts is mediated by PI3K p110a and mTORC2
Finlay et al., J Exp Med 2012 : The present study now demonstrates that mTORC1 activity in CD8 ( + ) T cells is not dependent on PI3K or Akt but is critical to sustain glucose uptake and glycolysis in CD8 ( + ) T cells
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
Razmara et al., Cell communication and signaling : CCS 2013 : 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
Jung et al., J Nutr Biochem 2013 : The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt dependent manner
Pang et al., World J Gastroenterol 2013 : Furthermore, TM treatment also activated mTORC1 , and in turn reduced Akt phosphorylation, which suggested the PI3K/Akt/mTOR signal pathway was involved in the TM-induced autophagic response in EC109 cells
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
Melnik et al., Exp Dermatol 2013 : Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling
Vadlakonda et al., Frontiers in oncology 2013 : We present in this article, a hypothesis that activation of Akt-T308 phosphorylation in the presence of high ATP : AMP ratio promotes the stability of its phosphorylations and activates mTORC1 and the energy consuming biosynthetic processes
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