KEGG   PATHWAY: aml04150
Entry
aml04150                    Pathway                                
Name
mTOR signaling pathway - Ailuropoda melanoleuca (giant panda)
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
aml04150  mTOR signaling pathway
aml04150

Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100468553  SLC7A5; large neutral amino acids transporter small subunit 1 [KO:K13780]
100465352  SLC3A2; 4F2 cell-surface antigen heavy chain [KO:K06519]
100481209  SLC38A9; sodium-coupled neutral amino acid transporter 9 isoform X2 [KO:K14995]
100472276  ATP6V1A; V-type proton ATPase catalytic subunit A isoform X1 [KO:K02145] [EC:7.1.2.2]
100482823  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
100463698  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
100464079  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X1 [KO:K02148]
100467928  ATP6V1C1; V-type proton ATPase subunit C 1 [KO:K02148]
100470452  ATP6V1D; V-type proton ATPase subunit D [KO:K02149]
100469216  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
100464522  ATP6V1E1; V-type proton ATPase subunit E 1 isoform X1 [KO:K02150]
100476784  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
100465872  ATP6V1G2; V-type proton ATPase subunit G 2 isoform X2 [KO:K02152]
100474366  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
100469813  ATP6V1G3; V-type proton ATPase subunit G 3 [KO:K02152]
100478019  ATP6V1H; V-type proton ATPase subunit H isoform X1 [KO:K02144]
100473830  LAMTOR1; ragulator complex protein LAMTOR1 [KO:K20397]
100464940  LAMTOR2; ragulator complex protein LAMTOR2 isoform X2 [KO:K20398]
100478518  LAMTOR3; ragulator complex protein LAMTOR3 isoform X1 [KO:K04370]
100469279  LAMTOR4; ragulator complex protein LAMTOR4 isoform X1 [KO:K20399]
100478871  LAMTOR5; ragulator complex protein LAMTOR5 [KO:K16344]
117800259  ragulator complex protein LAMTOR5-like [KO:K16344]
100470222  FLCN; folliculin isoform X1 [KO:K09594]
100480550  FNIP1; folliculin-interacting protein 1 isoform X1 [KO:K20400]
100483762  FNIP2; folliculin-interacting protein 2 isoform X2 [KO:K20401]
100469718  RRAGA; ras-related GTP-binding protein A [KO:K16185]
100474245  RRAGB; ras-related GTP-binding protein B isoform X1 [KO:K16185]
100478358  RRAGC; ras-related GTP-binding protein C isoform X2 [KO:K16186]
100484696  RRAGD; ras-related GTP-binding protein D [KO:K16186]
100469808  SESN2; sestrin-2 isoform X1 [KO:K20394]
100469914  CASTOR1; cytosolic arginine sensor for mTORC1 subunit 1 isoform X1 [KO:K23080]
100471935  CASTOR2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
100484356  MIOS; GATOR complex protein MIOS [KO:K20407]
105239157  SEH1L; nucleoporin SEH1 isoform X1 [KO:K14299]
100475224  WDR24; GATOR complex protein WDR24 [KO:K20408]
100478765  WDR59; GATOR complex protein WDR59 isoform X2 [KO:K20409]
100467863  SEC13; protein SEC13 homolog isoform X2 [KO:K14004]
100476450  DEPDC5; GATOR complex protein DEPDC5 isoform X1 [KO:K20404]
100464165  NPRL2; GATOR complex protein NPRL2 isoform X1 [KO:K20405]
100471022  NPRL3; GATOR complex protein NPRL3 isoform X3 [KO:K20406]
100480437  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
100463900  RNF152; E3 ubiquitin-protein ligase RNF152 [KO:K15705] [EC:2.3.2.27]
100478081  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
109489401  AKT1S1; proline-rich AKT1 substrate 1 [KO:K16184]
100471122  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100466507  DEPTOR; DEP domain-containing mTOR-interacting protein isoform X1 [KO:K20402]
100466513  MLST8; target of rapamycin complex subunit LST8 isoform X1 [KO:K08266]
100477972  TELO2; telomere length regulation protein TEL2 homolog [KO:K11137]
100473347  TTI1; TELO2-interacting protein 1 homolog isoform X1 [KO:K20403]
100468724  CLIP1; CAP-Gly domain-containing linker protein 1 isoform X6 [KO:K10421]
100476882  GRB10; growth factor receptor-bound protein 10 isoform X1 [KO:K20064]
100465923  LPIN1; phosphatidate phosphatase LPIN1 isoform X1 [KO:K15728] [EC:3.1.3.4]
100480077  LPIN3; phosphatidate phosphatase LPIN3 isoform X1 [KO:K15728] [EC:3.1.3.4]
100466187  LPIN2; phosphatidate phosphatase LPIN2 isoform X1 [KO:K15728] [EC:3.1.3.4]
100470276  ULK1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
100484867  ULK2; serine/threonine-protein kinase ULK2 isoform X1 [KO:K08269] [EC:2.7.11.1]
100469745  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100465592  EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259]
100483338  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
100463829  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
100484786  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100464998  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100466347  EIF4B; eukaryotic translation initiation factor 4B isoform X4 [KO:K03258]
100475057  RPS6; 40S ribosomal protein S6 [KO:K02991]
100472786  STRADA; STE20-related kinase adapter protein alpha isoform X2 [KO:K08271]
100473351  STRADB; STE20-related kinase adapter protein beta isoform X1 [KO:K17532]
100477412  STK11; serine/threonine-protein kinase STK11 isoform X4 [KO:K07298] [EC:2.7.11.1]
100477213  CAB39L; calcium-binding protein 39-like [KO:K08272]
100466814  CAB39; calcium-binding protein 39 [KO:K08272]
100481376  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
100470115  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
100471530  TSC1; hamartin isoform X1 [KO:K07206]
100465690  TSC2; tuberin isoform X1 [KO:K07207]
100470259  TBC1 domain family member 7 [KO:K20396]
100465977  RHEB; GTP-binding protein Rheb [KO:K07208]
100465789  DDIT4; DNA damage-inducible transcript 4 protein [KO:K08270]
100475007  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100480237  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
100481665  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
100471555  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100473835  WNT3A; protein Wnt-3a [KO:K00312]
100468584  WNT4; protein Wnt-4 [KO:K00408]
100484068  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100473854  WNT5B; protein Wnt-5b isoform X3 [KO:K00444]
100467896  WNT6; protein Wnt-6 [KO:K00445]
100475153  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
100474982  WNT7B; protein Wnt-7b [KO:K00572]
100466672  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
100481684  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
100472460  WNT9B; protein Wnt-9b [KO:K01064]
100475103  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
100467643  protein Wnt-10a isoform X1 [KO:K01357]
100475265  WNT10B; protein Wnt-10b isoform X1 [KO:K01357]
117795031  WNT10A; LOW QUALITY PROTEIN: protein Wnt-10a [KO:K01357]
100468561  WNT11; protein Wnt-11 [KO:K01384]
100464171  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
100469196  FZD1; frizzled-1 [KO:K02432]
109489608  FZD7; frizzled-7 [KO:K02432]
100469249  FZD2; frizzled-2 [KO:K02235]
100468831  FZD3; frizzled-3 isoform X1 [KO:K02329]
100470379  FZD4; frizzled-4 [KO:K02354]
100478649  FZD5; frizzled-5 [KO:K02375]
100467779  FZD8; frizzled-8 [KO:K02375]
100464621  FZD6; frizzled-6 isoform X1 [KO:K02376]
100479765  FZD10; frizzled-10 [KO:K02842]
100469765  FZD9; LOW QUALITY PROTEIN: frizzled-9 [KO:K02842]
100473379  LRP5; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 5 [KO:K03068]
100477840  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
100466067  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
100471972  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
100480005  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100479224  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100471563  TNF; tumor necrosis factor [KO:K03156]
100479926  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100471679  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100483432  INS; insulin isoform X2 [KO:K04526]
100473254  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
100473956  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
100471374  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100468916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
100474396  SOS2; son of sevenless homolog 2 isoform X9 [KO:K03099]
100482526  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100464196  NRAS; GTPase NRas [KO:K07828]
100469346  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100470572  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X7 [KO:K04373] [EC:2.7.11.1]
100474764  RPS6KA6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
100483843  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
100464040  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
100477645  IRS1; insulin receptor substrate 1 [KO:K16172]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100469483  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]
100473305  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100464675  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100481486  MAPKAP1; target of rapamycin complex 2 subunit MAPKAP1 isoform X5 [KO:K20410]
100464805  RICTOR; rapamycin-insensitive companion of mTOR isoform X4 [KO:K08267]
105239187  PRR5; proline-rich protein 5 isoform X1 [KO:K20411]
100482960  PRR5L; proline-rich protein 5-like isoform X1 [KO:K20411]
100476723  RHOA; transforming protein RhoA [KO:K04513]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100468926  SGK1; serine/threonine-protein kinase Sgk1 [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
aml00561  Glycerolipid metabolism
aml04010  MAPK signaling pathway
aml04140  Autophagy - animal
aml04151  PI3K-Akt signaling pathway
aml04152  AMPK signaling pathway
aml04810  Regulation of actin cytoskeleton
aml04910  Insulin signaling pathway
KO pathway
ko04150   
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