Gene interactions and pathways from curated databases and text-mining

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Pathways - manually collected, often from reviews:

  • KEGG Insulin signaling pathway: PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5 → MTOR (protein-protein, compound)
  • KEGG Type II diabetes mellitus: PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5 → MTOR (protein-protein, indirect effect)

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

Studies that report less than 10 interactions are marked with *

  • STRING interaction: PIK3R1 — MTOR (interaction, mapped from grid bind reactome kegg_pathways)
  • STRING interaction: MTOR — PIK3R1 (interaction, mapped from kegg_pathways)

Text-mined interactions from Literome

Sánchez-Margalet et al., J Cell Physiol 2000 : In order to study the role of phosphatidylinositol-3-kinase (PI3K), PKB, FRAP, S6 kinase, and MAP kinase in insulin stimulated glycogen synthesis, we used a specific inhibitor of PI3K , LY294002, the immunosuppressant inhibitor of FRAP , rapamycin, and the inhibitor of MAPK kinase ( MEK ) /MAPK, PD98059, in rat HTC hepatoma cells overexpressing human insulin receptors
Hou et al., J Neurosci 2004 : Two structurally unrelated PI3K inhibitors, LY294002 and wortmannin, blocked the DHPG induced increases in phosphorylation of Akt and mTOR ... Finally, we observed that both PI3K inhibitors and rapamycin, an mTOR inhibitor , prevented mGluR-LTD induced by DHPG
Li et al., Int J Biochem Cell Biol 2005 (MAP Kinase Signaling System) : Here we tested the hypothesis that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes ... Our results suggest that PI3K/Akt mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone treated myotubes
Shi et al., Mol Cancer Ther 2005 (Multiple Myeloma) : Thus, mTOR inhibitors activate PI3-K/AKT in multiple myeloma cells ; activation depends on basal IGF-R signaling ; and enhanced IRS-1/IGF-I receptor interactions secondary to inhibited IRS-1 serine phosphorylation may play a role in activation of the cascade
Bishop et al., J Endocrinol 2006 (Lymphoma) : In summary, PRL stimulated phosphorylation of mTOR is mediated by PI3K
Bussolati et al., J Mol Med (Berl) 2006 (Carcinoma, Renal Cell...) : As TEC were shown to display a basal upregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, we evaluated the possible regulation of TSP-1 by this pathway by using LY294002 and wortmannin, the PI3K inhibitors, and rapamycin, the mammalian target of rapamycin (mTOR) inhibitor
Zdychová et al., Experimental biology and medicine (Maywood, N.J.) 2008 (Diabetes Mellitus, Type 2...) : Acute PI3K inhibition with wortmannin ( 100 mug/kg ) attenuated renal Akt and mTOR activities in ZO, but not in ZL rats
Minhajuddin et al., J Biol Chem 2009 : Stimulation of human vascular endothelial cells with thrombin induced the phosphorylation of mTOR and its downstream target p70 S6 kinase in a PKC-delta- and PI3K/Akt dependent manner
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
Huang et al., Biochem Soc Trans 2009 : Through negative-feedback mechanisms, mTORC1 activity inhibits growth factor stimulation of PI3K
Balasubramanian et al., Cardiovasc Hematol Agents Med Chem 2009 (Cardiomegaly) : In pressure overloaded myocardium, adrenergic receptors, growth factor receptors, and integrins are known to activate mTOR in a PI3K dependent and/or independent manner with the involvement of specific PKC isoforms
Bhaskar et al., Molecular neurodegeneration 2009 : Finally, our results also demonstrate that Abeta oligomer treated neurons exhibit elevated levels of activated Akt and mTOR ( mammalian Target Of Rapamycin ) and that PI3K , Akt or mTOR inhibitors blocked Abeta oligomer induced neuronal CCEs
Gupta et al., Blood 2009 (Lymphoma, Follicular) : Activation of PI3K via APRIL results in phosphorylation of Akt and mammalian target of rapamycin (mTOR) and the mTOR-specific substrates p70S6 kinase and 4E-binding protein 1 in a TACI dependent manner
O'Neil et al., J Physiol 2009 (Mechanotransduction, Cellular) : Furthermore, inhibition of PI3K-PKB activity did not prevent the activation of mTOR signalling by ECs, indicating that PI3K-PKB is not part of the upstream regulatory pathway
Matheny et al., Biochem Biophys Res Commun 2009 : Our results collectively suggest that mTOR/p70S6K is activated in a PI3K/Akt dependent manner, but that in the absence of p110alpha or Akt, alternate pathway ( s ) may mediate activation of mTOR/p70S6K in C2C12 myoblasts
Lee et al., J Biol Chem 2010 : OSS also induced sustained activation of ERK, which was inhibited by the specific PI3K inhibitor LY294002 and was required for OSS induced activation of mTOR/p70S6K and proliferation in MG63 cells
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 ... However, as mTORC1 activation is independent of PI3K/AKT in acute myeloid leukemia, dual PI3K and mTOR inhibitors may induce apoptosis in blast cells
Tao et al., Journal of molecular signaling 2010 : Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside ( AICAR ) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1) associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin stimulated activation of mTOR was diminished ... Our present study demonstrates that AMPK exerts dual effects on the PI3K pathway, stimulating PI3K/Akt and inhibiting mTOR/S6K
Mason et al., IDrugs 2010 (Neoplasms) : This conference report highlights selected presentations on preclinical data on the novel pan-PI3K pyrimidine derived inhibitor BKM-120 ( Novartis AG ), the dual inhibition of mTOR/PI3K in NSCLC by PF-4691502 ( Pfizer Inc ), the small-molecule PDK-1 inhibitors PF-05177624 and PF-05197281 ( both Pfizer ) and the ability of RO-5323441 ( F Hoffmann-La Roche Ltd/ThromboGenics NV/BioInvent International AB ) to block tumor growth in vivo
Kim et al., J Lipid Res 2010 : 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 : However, the function and molecular mechanism of mTOR mediated PI3K signaling in B cells has not been fully elucidated
Tan et al., Cancer Cell 2010 (Cell Transformation, Neoplastic...) : On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1 dependent, but PI3K and AKT independent manner, resulting in resistance
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
Weigelt et al., Oncogene 2011 (Breast Neoplasms) : PI3K pathway activation leads to stimulation of the key growth and proliferation regulatory kinase mammalian target of rapamycin (mTOR) , which can be inhibited by rapamycin analogues and by kinase inhibitors ; the effectiveness of these drugs in breast cancer treatment is currently being tested in clinical trials
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
Wang et al., Oncogene 2012 (Ovarian Neoplasms) : LY294002 and GDC-0941, inhibitors of PI3K , or Rapamycin, an inhibitor of PI3K downstream target mTOR , can reverse the effects of Gab2 on migration and invasion
Li et al., J Immunol 2011 (HIV Infections...) : In this study we assessed in these macrophages if the blunted increase in TLR-4 mediated TNF-a release induced by lipid A ( LA ) is associated with PI3K induced upregulation of mammalian target of rapamycin (mTOR) activity
Gallagher et al., Oncogene 2012 (Cell Transformation, Neoplastic...) : We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia
Miller et al., Breast Cancer Res 2011 (Breast Neoplasms...) : PI3K activates AKT, serum/glucocorticoid regulated kinase ( SGK ), phosphoinositide dependent kinase 1 ( PDK1 ), mammalian target of rapamycin (mTOR) , and several other molecules involved in cell cycle progression and survival
Li et al., Methods Mol Biol 2012 (Disease Models, Animal...) : It is hoped that these inhibitors will have widespread clinical impact in oncology because mTOR is a major downstream effector of PI3K signaling, one of the most frequently activated pathways in cancer
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
Bhattacharya et al., Cancer Biol Ther 2012 (Stomach Neoplasms) : In AGS cells, PI3K inhibition alone enhanced 5-FU sensitivity as much as dual PI3K/mTOR inhibition
Zito et al., PloS one 2012 (Adenocarcinoma...) : Concurrent inhibition of PI3K and mTOR is synergistic in vitro, and a dual PI3K/mTOR inhibitor was highly active
Blaser et al., BMC cancer 2012 (Colonic Neoplasms) : LS174T, SW480 and DLD-1 colon cancer cell lines were treated with PP242 an ATP-competitive inhibitor of mTOR , NVP-BEZ235, a dual PI3K/mTOR inhibitor or rapamycin
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
Bridges et al., Mol Biol Cell 2012 : In this paper, we show that PIKFYVE and PI3K-C2a are necessary for activation of mTORC1 and its translocation to the plasma membrane in 3T3-L1 adipocytes
Shanmugasundaram et al., Oncogene 2013 (Carcinoma, Renal Cell...) : Here we provide additional genetic evidence that PI3K signaling activates mTORC2 kinase activity
Mitra et al., Cytokine 2012 (Arthritis...) : We observed that IL-22 induced significant proliferation of NHEK and FLS which was effectively inhibited by dual kinase ( PI3K/mTOR ) inhibitor, NVP-BEZ235 and specific mTOR inhibitor , Rapamycin
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
Ding et al., Tumour Biol 2013 (Colonic Neoplasms) : The PI3K inhibitor LY294002 inhibited both the phosphorylation of mTOR and upregulation of Livin
Zhu et al., Mol Endocrinol 2013 : Although short-term activation of PI3K and myrAkt1 increased mTOR and S6 signaling, there was no impairment in insulin mediated activation of IRS1/2
Razmara et al., Cell communication and signaling : CCS 2013 : Thus, whereas both mTORC1 and mTORC2 are activated in a PI3K dependent manner, different additional signaling pathways are needed ... Thus, whereas both mTORC1 and mTORC2 are activated in a PI3K dependent manner, different additional signaling pathways are needed
Fortress et al., Learn Mem 2013 (MAP Kinase Signaling System) : Collectively, these data demonstrate for the first time that activation of the dorsal hippocampal mTOR signaling pathway is necessary for E ( 2 ) to enhance object recognition memory consolidation and that E ( 2 ) -induced mTOR activation is dependent on upstream activation of ERK and PI3K signaling
Chung et al., J Endocrinol 2013 (MAP Kinase Signaling System) : Our data also suggest that PI3K/Akt mediated inactivation of GSK-3ß and activation of mTOR/p70 ( S6K ) contribute to the proliferative effect of ghrelin
Martinelli et al., Int J Cancer 2013 (Colorectal Neoplasms...) : The in vitro and in vivo anti-tumor activity of pimasertib, a selective MEK 1/2 inhibitor, alone or in combination with a PI3K inhibitor (PI3Ki) , a mTOR inhibitor ( everolimus ), or with multi targeted kinase inhibitors ( sorafenib and regorafenib ), that block also BRAF and CRAF, were tested in a panel of eight human lung and colon cancer cell lines
Xu et al., Mol Med Report 2013 : However, LY294002, a PI3K inhibitor, attenuated the anti-apoptotic effect of salidroside and blocked the increase of Akt and mTOR ; however, did not affect the antioxidative effect of salidroside
Berdichevsky et al., J Neurosci 2013 : Inhibition of PI3K and Akt prevented activation of mTOR , and was as effective as inhibition of mTOR in reducing ictal activity and cell death