KEGG   PATHWAY: uah04150
Entry
uah04150                    Pathway                                
Name
mTOR signaling pathway - Ursus arctos horribilis (North American brown bear)
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
uah04150  mTOR signaling pathway
uah04150

Organism
Ursus arctos horribilis (North American brown bear) [GN:uah]
Gene
113252161  SLC7A5; large neutral amino acids transporter small subunit 1 [KO:K13780]
113246945  SLC3A2; 4F2 cell-surface antigen heavy chain [KO:K06519]
113255326  SLC38A9; sodium-coupled neutral amino acid transporter 9 isoform X1 [KO:K14995]
113251490  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
113270020  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
113244182  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
113252853  ATP6V1C1; V-type proton ATPase subunit C 1 isoform X1 [KO:K02148]
113269864  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X1 [KO:K02148]
113248309  V-type proton ATPase subunit D [KO:K02149]
113248328  V-type proton ATPase subunit D isoform X1 [KO:K02149]
113258061  ATP6V1E1; V-type proton ATPase subunit E 1 [KO:K02150]
113246115  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
113263990  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
113242584  ATP6V1G3; V-type proton ATPase subunit G 3 [KO:K02152]
113243710  ATP6V1G2; V-type proton ATPase subunit G 2 isoform X1 [KO:K02152]
113266332  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
113268102  ATP6V1H; V-type proton ATPase subunit H [KO:K02144]
113269267  LAMTOR1; ragulator complex protein LAMTOR1 [KO:K20397]
113245250  LAMTOR2; ragulator complex protein LAMTOR2 [KO:K20398]
113263113  LAMTOR3; ragulator complex protein LAMTOR3 isoform X1 [KO:K04370]
113267876  LAMTOR4; ragulator complex protein LAMTOR4 isoform X1 [KO:K20399]
113244882  LAMTOR5; ragulator complex protein LAMTOR5 [KO:K16344]
113271307  FLCN; folliculin isoform X1 [KO:K09594]
113261697  FNIP1; folliculin-interacting protein 1 isoform X1 [KO:K20400]
113255806  FNIP2; folliculin-interacting protein 2 isoform X1 [KO:K20401]
113247969  RRAGB; ras-related GTP-binding protein B isoform X1 [KO:K16185]
113260596  RRAGA; ras-related GTP-binding protein A [KO:K16185]
113268259  RRAGC; ras-related GTP-binding protein C isoform X1 [KO:K16186]
113264828  RRAGD; ras-related GTP-binding protein D [KO:K16186]
113268419  SESN2; sestrin-2 [KO:K20394]
113245030  CASTOR1; cytosolic arginine sensor for mTORC1 subunit 1 isoform X1 [KO:K23080]
113267765  CASTOR2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
113260497  MIOS; GATOR complex protein MIOS isoform X1 [KO:K20407]
113245939  SEH1L; nucleoporin SEH1 isoform X1 [KO:K14299]
113245387  WDR24; GATOR complex protein WDR24 [KO:K20408]
113252489  WDR59; GATOR complex protein WDR59 isoform X1 [KO:K20409]
113257167  SEC13; protein SEC13 homolog isoform X1 [KO:K14004]
113245066  DEPDC5; GATOR complex protein DEPDC5 isoform X1 [KO:K20404]
113256913  NPRL2; GATOR complex protein NPRL2 isoform X1 [KO:K20405]
113245355  NPRL3; GATOR complex protein NPRL3 isoform X1 [KO:K20406]
113260895  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
113253477  RNF152; E3 ubiquitin-protein ligase RNF152 [KO:K15705] [EC:2.3.2.27]
113244532  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
113243278  AKT1S1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
113270510  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
113252772  DEPTOR; DEP domain-containing mTOR-interacting protein isoform X1 [KO:K20402]
113245112  MLST8; target of rapamycin complex subunit LST8 isoform X1 [KO:K08266]
113245086  TELO2; telomere length regulation protein TEL2 homolog isoform X1 [KO:K11137]
113258586  TTI1; TELO2-interacting protein 1 homolog [KO:K20403]
113266923  CLIP1; CAP-Gly domain-containing linker protein 1 isoform X1 [KO:K10421]
113257529  GRB10; growth factor receptor-bound protein 10 isoform X1 [KO:K20064]
113270025  LPIN1; phosphatidate phosphatase LPIN1 isoform X1 [KO:K15728] [EC:3.1.3.4]
113258611  LPIN3; phosphatidate phosphatase LPIN3 isoform X1 [KO:K15728] [EC:3.1.3.4]
113253253  LPIN2; phosphatidate phosphatase LPIN2 isoform X1 [KO:K15728] [EC:3.1.3.4]
113266853  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
113271267  ULK2; serine/threonine-protein kinase ULK2 isoform X1 [KO:K08269] [EC:2.7.11.1]
113262099  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
113263893  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
113263123  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
113250342  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
113244028  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
113268897  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
113257571  EIF4B; eukaryotic translation initiation factor 4B isoform X1 [KO:K03258]
113260592  RPS6; 40S ribosomal protein S6 [KO:K02991]
113265287  STRADA; STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
113250590  STRADB; STE20-related kinase adapter protein beta isoform X1 [KO:K17532]
113242722  STK11; serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
113250363  CAB39; calcium-binding protein 39 [KO:K08272]
113251318  CAB39L; calcium-binding protein 39-like [KO:K08272]
113260929  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
113254619  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
113266547  TSC1; hamartin isoform X1 [KO:K07206]
113245080  TSC2; tuberin isoform X1 [KO:K07207]
113264465  TBC1 domain family member 7 [KO:K20396]
113241493  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
113259157  DDIT4; DNA damage-inducible transcript 4 protein [KO:K08270]
113257365  WNT1; proto-oncogene Wnt-1 [KO:K03209]
113263284  WNT2; protein Wnt-2 [KO:K00182]
113244420  WNT2B; protein Wnt-2b [KO:K00182]
113265670  WNT3; proto-oncogene Wnt-3 [KO:K00312]
113247468  WNT3A; protein Wnt-3a [KO:K00312]
113268542  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
113258043  WNT5B; protein Wnt-5b [KO:K00444]
113256990  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
113250444  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
113241648  WNT7B; protein Wnt-7b [KO:K00572]
113257229  WNT7A; protein Wnt-7a [KO:K00572]
113261780  WNT8A; protein Wnt-8a [KO:K00714]
113251621  WNT8B; protein Wnt-8b [KO:K00714]
113247507  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
113257662  WNT10B; protein Wnt-10b [KO:K01357]
113248677  WNT10A; protein Wnt-10a [KO:K01357]
113269338  WNT11; protein Wnt-11 [KO:K01384]
113266506  WNT16; protein Wnt-16 [KO:K01558]
113259790  FZD1; frizzled-1 [KO:K02432]
113250581  FZD7; frizzled-7 [KO:K02432]
113265349  FZD2; frizzled-2 [KO:K02235]
113269945  FZD3; frizzled-3 isoform X1 [KO:K02329]
113269406  FZD4; frizzled-4 isoform X1 [KO:K02354]
113250522  FZD5; frizzled-5 [KO:K02375]
113244264  FZD8; frizzled-8 [KO:K02375]
113252851  FZD6; frizzled-6 [KO:K02376]
113267800  FZD9; frizzled-9 [KO:K02842]
113267107  FZD10; frizzled-10 [KO:K02842]
113257877  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
113244001  LRP5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
113254396  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
113270636  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
113271107  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
113251972  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
113243711  TNF; tumor necrosis factor [KO:K03156]
113257988  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
113245546  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
113243960  insulin-like [KO:K04526]
113256079  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
113242935  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
113263646  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
113244637  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
113266205  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
113241630  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
113257418  GTPase HRas-like [KO:K02833]
113257792  KRAS; GTPase KRas isoform X1 [KO:K07827]
113244394  NRAS; GTPase NRas [KO:K07828]
113265167  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
113257190  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
113240885  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
113242822  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
113267646  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
113247020  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113242238  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
113268455  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
113259645  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
113242134  RPS6KA6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
113250390  IRS1; insulin receptor substrate 1 [KO:K16172]
113256705  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113254730  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113255266  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113254799  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113270537  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113253989  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113258976  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
113245405  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
113267192  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
113243572  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113262966  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113251823  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
113266413  MAPKAP1; target of rapamycin complex 2 subunit MAPKAP1 isoform X1 [KO:K20410]
113260913  RICTOR; rapamycin-insensitive companion of mTOR isoform X1 [KO:K08267]
113241666  PRR5; proline-rich protein 5 isoform X1 [KO:K20411]
113265030  PRR5L; proline-rich protein 5-like isoform X1 [KO:K20411]
113256876  RHOA; transforming protein RhoA [KO:K04513]
113265250  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
113267584  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
113247385  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
113259468  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
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
uah00561  Glycerolipid metabolism
uah04010  MAPK signaling pathway
uah04140  Autophagy - animal
uah04151  PI3K-Akt signaling pathway
uah04152  AMPK signaling pathway
uah04810  Regulation of actin cytoskeleton
uah04910  Insulin signaling pathway
KO pathway
ko04150   
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