KEGG   PATHWAY: ko04150
Entry
ko04150                     Pathway                                
Name
mTOR signaling pathway
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
ko04150  mTOR signaling pathway
ko04150

Orthology
K00182  WNT2; wingless-type MMTV integration site family, member 2
K00312  WNT3; wingless-type MMTV integration site family, member 3
K00408  WNT4; wingless-type MMTV integration site family, member 4
K00444  WNT5; wingless-type MMTV integration site family, member 5
K00445  WNT6; wingless-type MMTV integration site family, member 6
K00572  WNT7; wingless-type MMTV integration site family, member 7
K00714  WNT8; wingless-type MMTV integration site family, member 8
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01064  WNT9; wingless-type MMTV integration site family, member 9
K01110  PTEN; phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K01357  WNT10; wingless-type MMTV integration site family, member 10
K01384  WNT11; wingless-type MMTV integration site family, member 11
K01558  WNT16; wingless-type MMTV integration site family, member 16
K02144  ATPeV1H; V-type H+-transporting ATPase subunit H
K02145  ATPeV1A, ATP6A; V-type H+-transporting ATPase subunit A [EC:7.1.2.2]
K02147  ATPeV1B, ATP6B; V-type H+-transporting ATPase subunit B
K02148  ATPeV1C, ATP6C; V-type H+-transporting ATPase subunit C
K02149  ATPeV1D, ATP6M; V-type H+-transporting ATPase subunit D
K02150  ATPeV1E, ATP6E; V-type H+-transporting ATPase subunit E
K02151  ATPeV1F, ATP6S14; V-type H+-transporting ATPase subunit F
K02152  ATPeV1G, ATP6G; V-type H+-transporting ATPase subunit G
K02235  FZD2; frizzled 2
K02329  FZD3; frizzled 3
K02353  DVL; segment polarity protein dishevelled
K02354  FZD4, fz4, CD344; frizzled 4
K02375  FZD5_8, fz2; frizzled 5/8
K02376  FZD6; frizzled 6
K02432  FZD1_7, fz; frizzled 1/7
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
K02842  FZD9_10, CD349_50; frizzled 9/10
K02991  RP-S6e, RPS6; small subunit ribosomal protein S6e
K03068  LRP5_6; low density lipoprotein receptor-related protein 5/6
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03099  SOS; son of sevenless
K03156  TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158  TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03209  WNT1; wingless-type MMTV integration site family, member 1
K03258  EIF4B; translation initiation factor 4B
K03259  EIF4E; translation initiation factor 4E
K03875  SKP2, FBXL1; F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2)
K04364  GRB2; growth factor receptor-bound protein 2
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04370  LAMTOR3, MP1, MAP2K1IP1; ragulator complex protein LAMTOR3
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04373  RPS6KA; ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04513  RHOA; Ras homolog gene family, member A
K04526  INS; insulin
K04527  INSR, CD220; insulin receptor [EC:2.7.10.1]
K04688  RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]
K04690  FZDN, fz3; frizzled
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05459  IGF1; insulin-like growth factor 1
K06276  PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K06519  SLC3A2, MDU1, CD98; solute carrier family 3, member 2
K07198  PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31]
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07204  RAPTOR; regulatory associated protein of mTOR
K07205  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1
K07206  TSC1; tuberous sclerosis 1
K07207  TSC2; tuberous sclerosis 2
K07208  RHEB; Ras homolog enriched in brain
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07298  STK11, LKB1; serine/threonine-protein kinase 11 [EC:2.7.11.1]
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K08266  MLST8, GBL; target of rapamycin complex subunit LST8
K08267  RICTOR; rapamycin-insensitive companion of mTOR
K08269  ULK2, ATG1; serine/threonine-protein kinase ULK2 [EC:2.7.11.1]
K08270  DDIT4, REDD1; DNA-damage-inducible transcript 4
K08271  STRADA, LYK5; STE20-related kinase adapter protein alpha
K08272  CAB39, MO25; calcium binding protein 39
K09594  FLCN, BHD; folliculin
K10421  CLIP1, RSN; CAP-Gly domain-containing linker protein 1
K11137  TELO2, TEL2; telomere length regulation protein
K13302  SGK1; serum/glucocorticoid-regulated kinase 1 [EC:2.7.11.1]
K13780  SLC7A5, LAT1; solute carrier family 7 (L-type amino acid transporter), member 5
K14004  SEC13; protein transport protein SEC13
K14299  SEH1; nucleoporin SEH1
K14995  SLC38A9; solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 9
K15705  RNF152; E3 ubiquitin-protein ligase RNF152 [EC:2.3.2.27]
K15728  LPIN; phosphatidate phosphatase LPIN [EC:3.1.3.4]
K16172  IRS1; insulin receptor substrate 1
K16184  AKT1S1, PRAS40; proline-rich AKT1 substrate 1
K16185  RRAGA_B; Ras-related GTP-binding protein A/B
K16186  RRAGC_D; Ras-related GTP-binding protein C/D
K16344  LAMTOR5, HBXIP; ragulator complex protein LAMTOR5
K17532  STRADB; STE20-related kinase adapter protein beta
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K20064  GRB10; growth factor receptor-bound protein 10
K20394  SESN2; sestrin 2
K20396  TBC1D7; TBC1 domain family member 7
K20397  LAMTOR1; ragulator complex protein LAMTOR1
K20398  LAMTOR2; ragulator complex protein LAMTOR2
K20399  LAMTOR4; ragulator complex protein LAMTOR4
K20400  FNIP1; folliculin-interacting protein 1
K20401  FNIP2; folliculin-interacting protein 2
K20402  DEPTOR; DEP domain-containing mTOR-interacting protein
K20403  TTI1; TELO2-interacting protein 1
K20404  DEPDC5, SEA1; SEA/GATOR complex protein SEA1/DEPDC5
K20405  NPRL2, NPR2; nitrogen permease regulator 2
K20406  NPRL3, NPR3; nitrogen permease regulator 3
K20407  MIOS, MIO, SEA4; SEA/GATOR complex protein SEA4/MIOS
K20408  WDR24, SEA2; SEA/GATOR complex protein SEA2/WDR24
K20409  WDR59, SEA3; SEA/GATOR complex protein SEA3/WDR59
K20410  MAPKAP1, SIN1, AVO1; target of rapamycin complex 2 subunit MAPKAP1/AVO1
K20411  PRR5, PROTOR; proline-rich protein 5
K21357  ULK1; serine/threonine-protein kinase ULK1 [EC:2.7.11.1]
K23080  CASTOR1; cytosolic arginine sensor for mTORC1 subunit 1
K23081  CASTOR2; cytosolic arginine sensor for mTORC1 subunit 2
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
ko00561  Glycerolipid metabolism
ko04010  MAPK signaling pathway
ko04140  Autophagy - animal
ko04151  PI3K-Akt signaling pathway
ko04152  AMPK signaling pathway
ko04810  Regulation of actin cytoskeleton
ko04910  Insulin signaling pathway

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