KEGG   PATHWAY: iti04150
Entry
iti04150                    Pathway                                
Name
mTOR signaling pathway - Ictidomys tridecemlineatus (thirteen-lined ground squirrel)
Description
The mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 contains mTOR, Raptor, PRAS40, Deptor, mLST8, Tel2 and Tti1. mTORC1 is activated by the presence of growth factors, amino acids, energy status, stress and oxygen levels to regulate several biological processes, including lipid metabolism, autophagy, protein synthesis and ribosome biogenesis. On the other hand, mTORC2, which consists of mTOR, mSin1, Rictor, Protor, Deptor, mLST8, Tel2 and Tti1, responds to growth factors and controls cytoskeletal organization, metabolism and survival.
Class
Environmental Information Processing; Signal transduction
Pathway map
iti04150  mTOR signaling pathway
iti04150

Organism
Ictidomys tridecemlineatus (thirteen-lined ground squirrel) [GN:iti]
Gene
101954994  Prkcb; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
101955107  Fzd8; frizzled-8 [KO:K02375]
101955124  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101955158  Depdc5; LOW QUALITY PROTEIN: GATOR complex protein DEPDC5 [KO:K20404]
101955315  Eif4e1b; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
101955399  Clip1; CAP-Gly domain-containing linker protein 1 isoform X1 [KO:K10421]
101955412  Sec13; protein SEC13 homolog isoform X1 [KO:K14004]
101955522  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101955606  Rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
101955906  Fzd1; frizzled-1 [KO:K02432]
101956506  Rps6ka1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
101956819  Atp6v1e1; V-type proton ATPase subunit E 1 [KO:K02150]
101956940  Fzd4; frizzled-4 [KO:K02354]
101956956  Prr5l; proline-rich protein 5-like isoform X2 [KO:K20411]
101957035  Nprl3; GATOR complex protein NPRL3 isoform X2 [KO:K20406]
101957141  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X2 [KO:K07198] [EC:2.7.11.31]
101957220  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101957333  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101957355  Atp6v1g3; V-type proton ATPase subunit G 3 [KO:K02152]
101957392  Pten; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
101957398  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101958580  Rheb; GTP-binding protein Rheb isoform X1 [KO:K07208]
101958971  Fnip2; folliculin-interacting protein 2 isoform X1 [KO:K20401]
101958982  Wnt5b; protein Wnt-5b [KO:K00444]
101959295  Slc38a9; sodium-coupled neutral amino acid transporter 9 isoform X1 [KO:K14995]
101959358  [KO:K04513]
101959359  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
101959379  Wnt4; protein Wnt-4 [KO:K00408]
101959456  Slc7a5; large neutral amino acids transporter small subunit 1 [KO:K13780]
101959540  Slc3a2; 4F2 cell-surface antigen heavy chain [KO:K06519]
101959569  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
101959574  Stradb; STE20-related kinase adapter protein beta isoform X1 [KO:K17532]
101959887  Wnt3a; protein Wnt-3a [KO:K00312]
101959985  Hras; GTPase HRas isoform X2 [KO:K02833]
101960014  Tti1; TELO2-interacting protein 1 homolog [KO:K20403]
101960094  Eif4b; eukaryotic translation initiation factor 4B [KO:K03258]
101960178  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
101960193  Cab39; calcium-binding protein 39 [KO:K08272]
101960366  [KO:K06519]
101960382  Wnt3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
101960744  Igf1r; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
101960867  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101960896  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
101961040  Wnt7a; protein Wnt-7a [KO:K00572]
101961151  Wnt8a; protein Wnt-8a [KO:K00714]
101961528  Rragd; ras-related GTP-binding protein D isoform X2 [KO:K16186]
101961593  Fzd7; frizzled-7 isoform X2 [KO:K02432]
101962141  Grb10; growth factor receptor-bound protein 10 isoform X2 [KO:K20064]
101962346  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X5 [KO:K06276] [EC:2.7.11.1]
101962360  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101962447  Flcn; folliculin [KO:K09594]
101962644  Ulk2; serine/threonine-protein kinase ULK2 isoform X2 [KO:K08269] [EC:2.7.11.1]
101962660  [KO:K00922] [EC:2.7.1.153]
101963110  Tsc1; hamartin isoform X1 [KO:K07206]
101963124  Sos2; son of sevenless homolog 2 [KO:K03099]
101963148  Cab39l; calcium-binding protein 39-like [KO:K08272]
101963152  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101963186  Wnt2b; protein Wnt-2b [KO:K00182]
101963246  Sgk1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
101963300  Wnt9a; protein Wnt-9a [KO:K01064]
101963540  Insr; insulin receptor [KO:K04527] [EC:2.7.10.1]
101963721  Wnt6; protein Wnt-6 [KO:K00445]
101963895  Atp6v1h; V-type proton ATPase subunit H isoform X1 [KO:K02144]
101964021  Wnt10a; protein Wnt-10a [KO:K01357]
101964030  Wnt8b; protein Wnt-8b [KO:K00714]
101964112  Fzd2; frizzled-2 [KO:K02235]
101964114  Kras; GTPase KRas isoform X1 [KO:K07827]
101964123  Lrp6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
101964140  Fzd6; frizzled-6 [KO:K02376]
101964638  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101964684  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101964890  Rraga; ras-related GTP-binding protein A [KO:K16185]
101964906  Lamtor5; ragulator complex protein LAMTOR5 [KO:K16344]
101964913  Tnf; tumor necrosis factor [KO:K03156]
101964938  Lamtor1; ragulator complex protein LAMTOR1 isoform X1 [KO:K20397]
101964990  Atp6v1c1; V-type proton ATPase subunit C 1 [KO:K02148]
101965489  Mlst8; target of rapamycin complex subunit LST8 isoform X3 [KO:K08266]
101965763  Ulk1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
101965886  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A isoform X3 [KO:K03158]
101965906  [KO:K00922] [EC:2.7.1.153]
101966062  Fzd5; frizzled-5 [KO:K02375]
101966207  Ins; insulin precursor [KO:K04526]
101966376  Atp6v1g2; V-type proton ATPase subunit G 2 isoform X1 [KO:K02152]
101966426  Rhoa; transforming protein RhoA [KO:K04513]
101966465  Rps6; 40S ribosomal protein S6 [KO:K02991]
101966517  [KO:K16344]
101966712  Irs1; insulin receptor substrate 1 [KO:K16172]
101966718  Wnt9b; protein Wnt-9b [KO:K01064]
101966789  [KO:K02145] [EC:7.1.2.2]
101966884  [KO:K03258]
101966958  [KO:K20409]
101967136  Sesn2; sestrin-2 isoform X2 [KO:K20394]
101967230  Akt1s1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
101967417  Tsc2; tuberin isoform X1 [KO:K07207]
101967677  Fzd9; frizzled-9 [KO:K02842]
101968140  Rps6ka6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
101968194  [KO:K02149]
101968353  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X3 [KO:K02353]
101968673  Deptor; DEP domain-containing mTOR-interacting protein [KO:K20402]
101968817  Nprl2; GATOR complex protein NPRL2 isoform X3 [KO:K20405]
101968890  Igf1; insulin-like growth factor I isoform X2 [KO:K05459]
101968896  [KO:K00922] [EC:2.7.1.153]
101969020  Atp6v1a; LOW QUALITY PROTEIN: V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
101969273  Rps6ka2; ribosomal protein S6 kinase alpha-2 isoform X3 [KO:K04373] [EC:2.7.11.1]
101969420  Lpin2; phosphatidate phosphatase LPIN2 [KO:K15728] [EC:3.1.3.4]
101969987  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101970053  Wnt10b; protein Wnt-10b [KO:K01357]
101970068  Castor2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
101970070  Atp6v1b2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
101970345  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
101970466  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101970679  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101970750  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101970789  Prr5; proline-rich protein 5 [KO:K20411]
101970848  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
101971045  Mios; GATOR complex protein MIOS isoform X1 [KO:K20407]
101971159  [KO:K04513]
101971244  Braf; serine/threonine-protein kinase B-raf isoform X5 [KO:K04365] [EC:2.7.11.1]
101971364  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101971474  Atp6v1b1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
101971504  Atp6v1c2; V-type proton ATPase subunit C 2 isoform X4 [KO:K02148]
101971833  Lrp5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
101971917  Strada; STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
101972098  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101972485  Lamtor4; ragulator complex protein LAMTOR4 isoform X3 [KO:K20399]
101972595  Wnt2; protein Wnt-2 [KO:K00182]
101972903  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101973050  Wdr24; GATOR complex protein WDR24 [KO:K20408]
101973150  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X2 [KO:K07198] [EC:2.7.11.31]
101973218  [KO:K02991]
101973561  Rps6ka3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
101974255  Atp6v1f; V-type proton ATPase subunit F [KO:K02151]
101974281  Rictor; rapamycin-insensitive companion of mTOR [KO:K08267]
101974557  Lpin1; phosphatidate phosphatase LPIN1 isoform X2 [KO:K15728] [EC:3.1.3.4]
101974689  Seh1l; nucleoporin SEH1 [KO:K14299]
101974705  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101974776  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101975144  Wnt16; protein Wnt-16 [KO:K01558]
101975221  Ddit4; DNA damage-inducible transcript 4 protein [KO:K08270]
101975406  Lamtor3; ragulator complex protein LAMTOR3 [KO:K04370]
101975616  Stk11; serine/threonine-protein kinase STK11 isoform X5 [KO:K07298] [EC:2.7.11.1]
101975667  Mapkap1; target of rapamycin complex 2 subunit MAPKAP1 isoform X1 [KO:K20410]
101975679  Rnf152; E3 ubiquitin-protein ligase RNF152 [KO:K15705] [EC:2.3.2.27]
101975689  Skp2; S-phase kinase-associated protein 2 isoform X4 [KO:K03875]
101975873  Atp6v1e2; V-type proton ATPase subunit E 2 [KO:K02150]
101975906  Nras; GTPase NRas [KO:K07828]
101976072  Lamtor2; ragulator complex protein LAMTOR2 [KO:K20398]
101976082  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101976353  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101976552  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101976944  Fzd3; frizzled-3 isoform X1 [KO:K02329]
101976947  Telo2; telomere length regulation protein TEL2 homolog [KO:K11137]
101977253  Atp6v1g1; V-type proton ATPase subunit G 1 [KO:K02152]
101977590  Fzd10; frizzled-10 [KO:K02842]
101977628  Castor1; cytosolic arginine sensor for mTORC1 subunit 1 [KO:K23080]
101977696  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
101977707  Rragb; ras-related GTP-binding protein B isoform X1 [KO:K16185]
101977828  Eif4e; eukaryotic translation initiation factor 4E isoform X3 [KO:K03259]
101978230  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101978245  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101978324  Fnip1; folliculin-interacting protein 1 isoform X1 [KO:K20400]
101978587  Eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
101978692  Lpin3; phosphatidate phosphatase LPIN3 isoform X2 [KO:K15728] [EC:3.1.3.4]
120883648  Rragc; ras-related GTP-binding protein C isoform X1 [KO:K16186]
120884463  [KO:K16344]
120886432  Atp6v1d; V-type proton ATPase subunit D [KO:K02149]
120889960  [KO:K02991]
Compound
C00020  AMP
C00062  L-Arginine
C00123  L-Leucine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:27304501
  Authors
Kennedy BK, Lamming DW
  Title
The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging.
  Journal
Cell Metab 23:990-1003 (2016)
DOI:10.1016/j.cmet.2016.05.009
Reference
PMID:24556838
  Authors
Shimobayashi M, Hall MN
  Title
Making new contacts: the mTOR network in metabolism and signalling crosstalk.
  Journal
Nat Rev Mol Cell Biol 15:155-62 (2014)
DOI:10.1038/nrm3757
Reference
PMID:25242279
  Authors
Huang K, Fingar DC
  Title
Growing knowledge of the mTOR signaling network.
  Journal
Semin Cell Dev Biol 36:79-90 (2014)
DOI:10.1016/j.semcdb.2014.09.011
Reference
PMID:26269525
  Authors
Bockaert J, Marin P
  Title
mTOR in Brain Physiology and Pathologies.
  Journal
Physiol Rev 95:1157-87 (2015)
DOI:10.1152/physrev.00038.2014
Reference
PMID:26185979
  Authors
Caron A, Richard D, Laplante M
  Title
The Roles of mTOR Complexes in Lipid Metabolism.
  Journal
Annu Rev Nutr 35:321-48 (2015)
DOI:10.1146/annurev-nutr-071714-034355
Reference
PMID:26658722
  Authors
Shimobayashi M, Hall MN
  Title
Multiple amino acid sensing inputs to mTORC1.
  Journal
Cell Res 26:7-20 (2016)
DOI:10.1038/cr.2015.146
Reference
PMID:24698685
  Authors
Bar-Peled L, Sabatini DM
  Title
Regulation of mTORC1 by amino acids.
  Journal
Trends Cell Biol 24:400-6 (2014)
DOI:10.1016/j.tcb.2014.03.003
Reference
PMID:26046644
  Authors
Fingar DC
  Title
Rag Ubiquitination Recruits a GATOR1: Attenuation of Amino Acid-Induced mTORC1 Signaling.
  Journal
Mol Cell 58:713-5 (2015)
DOI:10.1016/j.molcel.2015.05.029
Reference
PMID:26700098
  Authors
Cai H, Dong LQ, Liu F
  Title
Recent Advances in Adipose mTOR Signaling and Function: Therapeutic Prospects.
  Journal
Trends Pharmacol Sci 37:303-17 (2016)
DOI:10.1016/j.tips.2015.11.011
Reference
PMID:24842496
  Authors
Eyre TA, Collins GP, Goldstone AH, Cwynarski K
  Title
Time now to TORC the TORC? New developments in mTOR pathway inhibition in lymphoid malignancies.
  Journal
Br J Haematol 166:336-51 (2014)
DOI:10.1111/bjh.12945
Reference
PMID:23465396
  Authors
Jewell JL, Guan KL
  Title
Nutrient signaling to mTOR and cell growth.
  Journal
Trends Biochem Sci 38:233-42 (2013)
DOI:10.1016/j.tibs.2013.01.004
Reference
PMID:23421405
  Authors
Wood TL, Bercury KK, Cifelli SE, Mursch LE, Min J, Dai J, Macklin WB
  Title
mTOR: a link from the extracellular milieu to transcriptional regulation of oligodendrocyte development.
  Journal
ASN Neuro 5:e00108 (2013)
DOI:10.1042/AN20120092
Reference
PMID:23694989
  Authors
Kim SG, Buel GR, Blenis J
  Title
Nutrient regulation of the mTOR complex 1 signaling pathway.
  Journal
Mol Cells 35:463-73 (2013)
DOI:10.1007/s10059-013-0138-2
Reference
PMID:19812304
  Authors
Laplante M, Sabatini DM
  Title
mTOR signaling at a glance.
  Journal
J Cell Sci 122:3589-94 (2009)
DOI:10.1242/jcs.051011
Reference
PMID:16756488
  Authors
Alessi DR, Sakamoto K, Bayascas JR
  Title
LKB1-dependent signaling pathways.
  Journal
Annu Rev Biochem 75:137-63 (2006)
DOI:10.1146/annurev.biochem.75.103004.142702
Reference
PMID:27027448
  Authors
Dan HC, Antonia RJ, Baldwin AS
  Title
PI3K/Akt promotes feedforward mTORC2 activation through IKKalpha.
  Journal
Oncotarget 7:21064-75 (2016)
DOI:10.18632/oncotarget.8383
Reference
PMID:28283069
  Authors
Saxton RA, Sabatini DM
  Title
mTOR Signaling in Growth, Metabolism, and Disease.
  Journal
Cell 168:960-976 (2017)
DOI:10.1016/j.cell.2017.02.004
Related
pathway
iti00561  Glycerolipid metabolism
iti04010  MAPK signaling pathway
iti04140  Autophagy - animal
iti04151  PI3K-Akt signaling pathway
iti04152  AMPK signaling pathway
iti04810  Regulation of actin cytoskeleton
iti04910  Insulin signaling pathway
KO pathway
ko04150   

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