KEGG   PATHWAY: oas04150
Entry
oas04150                    Pathway                                
Name
mTOR signaling pathway - Ovis aries (sheep)
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
oas04150  mTOR signaling pathway
oas04150

Organism
Ovis aries (sheep) [GN:oas]
Gene
100037665  RPS6; small ribosomal subunit protein eS6 [KO:K02991]
100126577  WNT2; protein Wnt-2 precursor [KO:K00182]
100127210  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
100135698  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
100169938  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
100271659  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100302067  RRAGA; ras-related GTP-binding protein A [KO:K16185]
100302069  RHEB; GTP-binding protein Rheb [KO:K07208]
100302070  RRAGC; ras-related GTP-binding protein C [KO:K16186]
100302078  RHOA; transforming protein RhoA [KO:K04513]
100302087  STRADA; STE20-related kinase adapter protein alpha [KO:K08271]
101101932  FZD4; frizzled-4 [KO:K02354]
101102025  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
101102060  WNT9A; protein Wnt-9a [KO:K01064]
101102293  IRS1; insulin receptor substrate 1 [KO:K16172]
101102299  WNT10B; protein Wnt-10b [KO:K01357]
101102438  NRAS; GTPase NRas [KO:K07828]
101102659  ATP6V1G3; V-type proton ATPase subunit G 3 [KO:K02152]
101102732  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
101103218  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X2 [KO:K03259]
101103229  WNT16; protein Wnt-16 [KO:K01558]
101103310  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X1 [KO:K02148]
101103389  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101103425  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
101103451  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
101103546  FZD7; frizzled-7 [KO:K02432]
101103830  TTI1; TELO2-interacting protein 1 homolog [KO:K20403]
101104259  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
101104430  DEPDC5; GATOR1 complex protein DEPDC5 isoform X1 [KO:K20404]
101104613  TBC1D7; TBC1 domain family member 7 isoform X1 [KO:K20396]
101105528  RICTOR; rapamycin-insensitive companion of mTOR isoform X2 [KO:K08267]
101105666  [KO:K02991]
101106246  [KO:K04513]
101106260  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
101106309  CAB39; calcium-binding protein 39 [KO:K08272]
101106450  LPIN3; phosphatidate phosphatase LPIN3 isoform X1 [KO:K15728] [EC:3.1.3.4]
101106878  PRR5L; proline-rich protein 5-like isoform X1 [KO:K20411]
101106991  LAMTOR4; ragulator complex protein LAMTOR4 isoform X2 [KO:K20399]
101107371  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101107438  BRAF; serine/threonine-protein kinase B-raf isoform X3 [KO:K04365] [EC:2.7.11.1]
101107683  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
101107685  EIF4B; eukaryotic translation initiation factor 4B isoform X4 [KO:K03258]
101107709  SGK1; serine/threonine-protein kinase Sgk1 isoform X3 [KO:K13302] [EC:2.7.11.1]
101107847  RRAGB; ras-related GTP-binding protein B isoform X2 [KO:K16185]
101107926  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
101108044  WNT8A; protein Wnt-8a [KO:K00714]
101108239  ULK2; serine/threonine-protein kinase ULK2 isoform X3 [KO:K08269] [EC:2.7.11.1]
101108549  STRADB; STE20-related kinase adapter protein beta [KO:K17532]
101109114  AKT1S1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
101109236  TELO2; telomere length regulation protein TEL2 homolog isoform X2 [KO:K11137]
101109483  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
101109531  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
101109574  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101109745  WNT5A; protein Wnt-5a [KO:K00444]
101109759  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101109893  GRB2; growth factor receptor-bound protein 2 isoform X5 [KO:K04364]
101110015  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101110043  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
101110074  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101110124  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
101110413  LAMTOR3; ragulator complex protein LAMTOR3 [KO:K04370]
101110659  SESN2; sestrin-2 [KO:K20394]
101111048  WNT11; protein Wnt-11 [KO:K01384]
101111143  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101111239  LAMTOR5; ragulator complex protein LAMTOR5 [KO:K16344]
101111275  GRB10; growth factor receptor-bound protein 10 isoform X1 [KO:K20064]
101111426  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 isoform X6 [KO:K07205]
101111428  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X2 [KO:K04373] [EC:2.7.11.1]
101111546  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101111785  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
101111832  FNIP2; folliculin-interacting protein 2 isoform X1 [KO:K20401]
101112277  CASTOR2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
101112309  FZD1; frizzled-1 [KO:K02432]
101112724  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
101112730  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
101112971  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
101113129  WNT10A; protein Wnt-10a [KO:K01357]
101113504  ATP6V1H; V-type proton ATPase subunit H isoform X2 [KO:K02144]
101113714  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
101113846  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101114005  KRAS; GTPase KRas isoform X1 [KO:K07827]
101114114  RRAGD; ras-related GTP-binding protein D isoform X1 [KO:K16186]
101114236  FZD9; frizzled-9 [KO:K02842]
101114389  SLC38A9; neutral amino acid transporter 9 isoform X1 [KO:K14995]
101114530  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
101114584  DDIT4; DNA damage-inducible transcript 4 protein [KO:K08270]
101114666  MLST8; target of rapamycin complex subunit LST8 isoform X1 [KO:K08266]
101115088  TSC2; tuberin isoform X1 [KO:K07207]
101115392  WDR59; GATOR complex protein WDR59 isoform X4 [KO:K20409]
101115485  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
101115803  CAB39L; calcium-binding protein 39-like isoform X1 [KO:K08272]
101116423  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101116777  [KO:K02149]
101116778  SLC3A2; amino acid transporter heavy chain SLC3A2 isoform X1 [KO:K06519]
101116782  WNT2B; protein Wnt-2b [KO:K00182]
101116863  [KO:K02991]
101117211  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
101117245  STK11; serine/threonine-protein kinase STK11 isoform X2 [KO:K07298] [EC:2.7.11.1]
101117348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101117599  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353]
101117701  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
101118410  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101118462  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101118762  FZD5; frizzled-5 [KO:K02375]
101118865  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
101118991  FZD10; frizzled-10 [KO:K02842]
101119127  TSC1; hamartin isoform X1 [KO:K07206]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101119321  RPTOR; regulatory-associated protein of mTOR isoform X4 [KO:K07204]
101119351  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]
101119502  LAMTOR1; ragulator complex protein LAMTOR1 [KO:K20397]
101120096  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101120627  NPRL3; GATOR1 complex protein NPRL3 isoform X1 [KO:K20406]
101120647  LPIN1; phosphatidate phosphatase LPIN1 [KO:K15728] [EC:3.1.3.4]
101120700  NPRL2; GATOR1 complex protein NPRL2 [KO:K20405]
101120784  SEC13; protein SEC13 homolog isoform X2 [KO:K14004]
101120823  MIOS; GATOR complex protein MIOS [KO:K20407]
101121120  CLIP1; CAP-Gly domain-containing linker protein 1 isoform X2 [KO:K10421]
101121176  ATP6V1D; V-type proton ATPase subunit D isoform X1 [KO:K02149]
101121415  WNT5B; protein Wnt-5b isoform X2 [KO:K00444]
101121455  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101121814  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
101121915  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X8 [KO:K04373] [EC:2.7.11.1]
101121947  FLCN; folliculin isoform X1 [KO:K09594]
101122197  FZD6; frizzled-6 [KO:K02376]
101122423  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
101122445  ATP6V1C1; V-type proton ATPase subunit C 1 isoform X1 [KO:K02148]
101122727  CASTOR1; cytosolic arginine sensor for mTORC1 subunit 1 isoform X2 [KO:K23080]
101122907  LAMTOR2; ragulator complex protein LAMTOR2 isoform X2 [KO:K20398]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101123247  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101123258  LPIN2; phosphatidate phosphatase LPIN2 isoform X1 [KO:K15728] [EC:3.1.3.4]
101123298  FNIP1; folliculin-interacting protein 1 isoform X2 [KO:K20400]
101123332  ATP6V1G2; V-type proton ATPase subunit G 2 [KO:K02152]
101123374  WNT3A; protein Wnt-3a [KO:K00312]
101123606  [KO:K02149]
101123635  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
105602663  [KO:K02991]
105610424  WDR24; GATOR complex protein WDR24 [KO:K20408]
106991797  [KO:K02991]
106991878  RNF152; E3 ubiquitin-protein ligase RNF152 [KO:K15705] [EC:2.3.2.27]
106992034  DEPTOR; DEP domain-containing mTOR-interacting protein isoform X1 [KO:K20402]
114109341  WNT7A; protein Wnt-7a [KO:K00572]
114110058  [KO:K04364]
114110121  INS; insulin [KO:K04526]
114110468  SEH1L; nucleoporin SEH1 isoform X1 [KO:K14299]
114110622  [KO:K02329]
114114092  PRR5; proline-rich protein 5 isoform X1 [KO:K20411]
114114919  [KO:K02833]
114116599  [KO:K02991]
114116812  [KO:K04513]
114117561  FZD8; frizzled-8 [KO:K02375]
114118688  [KO:K02991]
121818294  [KO:K16344]
121819715  [KO:K02991]
121820714  WNT9B; protein Wnt-9b [KO:K01064]
443249  SLC7A5; large neutral amino acids transporter small subunit 1 [KO:K13780]
443294  MAPKAP1; target of rapamycin complex 2 subunit MAPKAP1 [KO:K20410]
443318  IGF1; insulin-like growth factor I precursor [KO:K05459]
443431  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
443515  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
443540  TNF; tumor necrosis factor [KO:K03156]
494438  ATP6V1E1; V-type proton ATPase subunit E 1 [KO:K02150]
494439  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
780481  FZD2; frizzled-2 [KO:K02235]
780482  FZD3; frizzled-3 isoform X1 [KO:K02329]
780484  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
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
oas00561  Glycerolipid metabolism
oas04010  MAPK signaling pathway
oas04140  Autophagy - animal
oas04151  PI3K-Akt signaling pathway
oas04152  AMPK signaling pathway
oas04810  Regulation of actin cytoskeleton
oas04910  Insulin signaling pathway
KO pathway
ko04150   

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