KEGG   PATHWAY: hsa04150
Entry
hsa04150                    Pathway                                
Name
mTOR signaling pathway - Homo sapiens (human)
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
hsa04150  mTOR signaling pathway
hsa04150

Network
nt06166  Human papillomavirus (HPV)
nt06167  Human cytomegalovirus (HCMV)
nt06168  Herpes simplex virus 1 (HSV-1)
nt06522  mTOR signaling
  Element
N00582  IGF-IGF1R-PI3K signaling pathway
N01575  TSC1/2-mTORC1 signaling pathway
N01576  STRAD/STK11- TSC signaling pathway
N01578  GATOR1-mTORC1 signaling pathway
N01584  FLCN-mTORC1 signaling pathway
Drug
D00753  Sirolimus (JAN/USAN/INN)
D02714  Everolimus (JAN/USAN/INN)
D05393  Pegsunercept (USAN)
D06068  Temsirolimus (JAN/USAN/INN)
D06221  Triciribine phosphate (USAN)
D06669  Zotarolimus (USAN/INN)
D08900  Ridaforolimus (JAN/USAN/INN)
D10076  Olcorolimus (USAN)
D11183  Sapanisertib (USAN/INN)
D11440  Bimiralisib (USAN/INN)
D11501  Samotolisib (USAN)
D11663  Onatasertib (USAN)
D11869  Paxalisib (USAN/INN)
D12443  Nanvuranlat hydrochloride hydrate (JAN)
D12952  Veligrotug (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
101927180  ATP6V1FP2; V-type proton ATPase subunit F-like [KO:K02151]
10325  RRAGB; Ras related GTP binding B [KO:K16185]
10542  LAMTOR5; late endosomal/lysosomal adaptor, MAPK and MTOR activator 5 [KO:K16344]
10641  NPRL2; NPR2 like, GATOR1 complex subunit [KO:K20405]
10670  RRAGA; Ras related GTP binding A [KO:K16185]
107080638  [KO:K20396]
110117499  P3R3URF-PIK3R3; P3R3URF-PIK3R3 readthrough [KO:K02649]
11211  FZD10; frizzled class receptor 10 [KO:K02842]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
127124  ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152]
153129  SLC38A9; solute carrier family 38 member 9 [KO:K14995]
1855  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
1856  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1857  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1975  EIF4B; eukaryotic translation initiation factor 4B [KO:K03258]
1977  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
1978  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
201163  FLCN; folliculin [KO:K09594]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
220441  RNF152; ring finger protein 152 [KO:K15705] [EC:2.3.2.27]
23175  LPIN1; lipin 1 [KO:K15728] [EC:3.1.3.4]
245973  ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148]
2475  MTOR; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
253260  RICTOR; RPTOR independent companion of MTOR complex 2 [KO:K08267]
253314  EIF4E1B; eukaryotic translation initiation factor 4E family member 1B [KO:K03259]
2535  FZD2; frizzled class receptor 2 [KO:K02235]
27330  RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
2887  GRB10; growth factor receptor bound protein 10 [KO:K20064]
28956  LAMTOR2; late endosomal/lysosomal adaptor, MAPK and MTOR activator 2 [KO:K20398]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3479  IGF1; insulin like growth factor 1 [KO:K05459]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
3630  INS; insulin [KO:K04526]
3643  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
3667  IRS1; insulin receptor substrate 1 [KO:K16172]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
387  RHOA; ras homolog family member A [KO:K04513]
389541  LAMTOR4; late endosomal/lysosomal adaptor, MAPK and MTOR activator 4 [KO:K20399]
4040  LRP6; LDL receptor related protein 6 [KO:K03068]
4041  LRP5; LDL receptor related protein 5 [KO:K03068]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
51256  TBC1D7; TBC1 domain family member 7 [KO:K20396]
51382  ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149]
51384  WNT16; Wnt family member 16 [KO:K01558]
51606  ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]
5170  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
51719  CAB39; calcium binding protein 39 [KO:K08272]
523  ATP6V1A; ATPase H+ transporting V1 subunit A [KO:K02145] [EC:7.1.2.2]
525  ATP6V1B1; ATPase H+ transporting V1 subunit B1 [KO:K02147]
526  ATP6V1B2; ATPase H+ transporting V1 subunit B2 [KO:K02147]
528  ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148]
529  ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
534  ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152]
54361  WNT4; Wnt family member 4 [KO:K00408]
54468  MIOS; meiosis regulator for oocyte development [KO:K20407]
54541  DDIT4; DNA damage inducible transcript 4 [KO:K08270]
55004  LAMTOR1; late endosomal/lysosomal adaptor, MAPK and MTOR activator 1 [KO:K20397]
55437  STRADB; STE20 related adaptor beta [KO:K17532]
55615  PRR5; proline rich 5 [KO:K20411]
5562  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
5563  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
5578  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
5579  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5728  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
57521  RPTOR; regulatory associated protein of MTOR complex 1 [KO:K07204]
57600  FNIP2; folliculin interacting protein 2 [KO:K20401]
58528  RRAGD; Ras related GTP binding D [KO:K16186]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
6009  RHEB; Ras homolog, mTORC1 binding [KO:K07208]
6194  RPS6; ribosomal protein S6 [KO:K02991]
6195  RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
6196  RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
6197  RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
6198  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
6199  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
6249  CLIP1; CAP-Gly domain containing linker protein 1 [KO:K10421]
6396  SEC13; SEC13 homolog, nuclear pore and COPII coat complex component [KO:K14004]
64121  RRAGC; Ras related GTP binding C [KO:K16186]
64223  MLST8; MTOR associated protein, LST8 homolog [KO:K08266]
6446  SGK1; serum/glucocorticoid regulated kinase 1 [KO:K13302] [EC:2.7.11.1]
64798  DEPTOR; DEP domain containing MTOR interacting protein [KO:K20402]
64900  LPIN3; lipin 3 [KO:K15728] [EC:3.1.3.4]
6502  SKP2; S-phase kinase associated protein 2 [KO:K03875]
6520  SLC3A2; solute carrier family 3 member 2 [KO:K06519]
652968  CASTOR1; cytosolic arginine sensor for mTORC1 subunit 1 [KO:K23080]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
6794  STK11; serine/threonine kinase 11 [KO:K07298] [EC:2.7.11.1]
7124  TNF; tumor necrosis factor [KO:K03156]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
7248  TSC1; TSC complex subunit 1 [KO:K07206]
7249  TSC2; TSC complex subunit 2 [KO:K07207]
729438  CASTOR2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
7471  WNT1; Wnt family member 1 [KO:K03209]
7472  WNT2; Wnt family member 2 [KO:K00182]
7473  WNT3; Wnt family member 3 [KO:K00312]
7474  WNT5A; Wnt family member 5A [KO:K00444]
7475  WNT6; Wnt family member 6 [KO:K00445]
7476  WNT7A; Wnt family member 7A [KO:K00572]
7477  WNT7B; Wnt family member 7B [KO:K00572]
7478  WNT8A; Wnt family member 8A [KO:K00714]
7479  WNT8B; Wnt family member 8B [KO:K00714]
7480  WNT10B; Wnt family member 10B [KO:K01357]
7481  WNT11; Wnt family member 11 [KO:K01384]
7482  WNT2B; Wnt family member 2B [KO:K00182]
7483  WNT9A; Wnt family member 9A [KO:K01064]
7484  WNT9B; Wnt family member 9B [KO:K01064]
7855  FZD5; frizzled class receptor 5 [KO:K02375]
79109  MAPKAP1; MAPK associated protein 1 [KO:K20410]
79726  WDR59; WD repeat domain 59 [KO:K20409]
7976  FZD3; frizzled class receptor 3 [KO:K02329]
79899  PRR5L; proline rich 5 like [KO:K20411]
80326  WNT10A; Wnt family member 10A [KO:K01357]
81029  WNT5B; Wnt family member 5B [KO:K00444]
8131  NPRL3; NPR3 like, GATOR1 complex subunit [KO:K20406]
8140  SLC7A5; solute carrier family 7 member 5 [KO:K13780]
81617  CAB39L; calcium binding protein 39 like [KO:K08272]
81929  SEH1L; SEH1 like nucleoporin [KO:K14299]
8321  FZD1; frizzled class receptor 1 [KO:K02432]
8322  FZD4; frizzled class receptor 4 [KO:K02354]
8323  FZD6; frizzled class receptor 6 [KO:K02376]
8324  FZD7; frizzled class receptor 7 [KO:K02432]
8325  FZD8; frizzled class receptor 8 [KO:K02375]
8326  FZD9; frizzled class receptor 9 [KO:K02842]
83667  SESN2; sestrin 2 [KO:K20394]
8408  ULK1; unc-51 like autophagy activating kinase 1 [KO:K21357] [EC:2.7.11.1]
84219  WDR24; WD repeat domain 24 [KO:K20408]
84335  AKT1S1; AKT1 substrate 1 [KO:K16184]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
8649  LAMTOR3; late endosomal/lysosomal adaptor, MAPK and MTOR activator 3 [KO:K04370]
89780  WNT3A; Wnt family member 3A [KO:K00312]
90423  ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150]
92335  STRADA; STE20 related adaptor alpha [KO:K08271]
9296  ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151]
9470  EIF4E2; eukaryotic translation initiation factor 4E family member 2 [KO:K03259]
9550  ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152]
96459  FNIP1; folliculin interacting protein 1 [KO:K20400]
9663  LPIN2; lipin 2 [KO:K15728] [EC:3.1.3.4]
9675  TTI1; TELO2 interacting protein 1 [KO:K20403]
9681  DEPDC5; DEP domain containing 5, GATOR1 subcomplex subunit [KO:K20404]
9706  ULK2; unc-51 like autophagy activating kinase 2 [KO:K08269] [EC:2.7.11.1]
9894  TELO2; telomere maintenance 2 [KO:K11137]
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
hsa00561  Glycerolipid metabolism
hsa04010  MAPK signaling pathway
hsa04140  Autophagy - animal
hsa04151  PI3K-Akt signaling pathway
hsa04152  AMPK signaling pathway
hsa04810  Regulation of actin cytoskeleton
hsa04910  Insulin signaling pathway
KO pathway
ko04150   

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