KEGG   PATHWAY: opi04150
Entry
opi04150                    Pathway                                
Name
mTOR signaling pathway - Ochotona princeps (American pika)
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
opi04150  mTOR signaling pathway
opi04150

Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101531654  SLC7A5; large neutral amino acids transporter small subunit 1 [KO:K13780]
101526843  SLC3A2; 4F2 cell-surface antigen heavy chain [KO:K06519]
101523029  SLC38A9; sodium-coupled neutral amino acid transporter 9 isoform X1 [KO:K14995]
101517947  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
101526960  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
101526254  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
101520647  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X2 [KO:K02148]
101526790  ATP6V1C1; V-type proton ATPase subunit C 1 isoform X2 [KO:K02148]
101522950  ATP6V1D; V-type proton ATPase subunit D [KO:K02149]
101520811  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
101530705  ATP6V1E1; V-type proton ATPase subunit E 1 [KO:K02150]
101529972  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
101526448  ATP6V1G2; V-type proton ATPase subunit G 2 isoform X1 [KO:K02152]
101530906  ATP6V1G3; V-type proton ATPase subunit G 3 [KO:K02152]
101528503  ATP6V1G1; V-type proton ATPase subunit G 1 isoform X1 [KO:K02152]
101516815  ATP6V1H; V-type proton ATPase subunit H [KO:K02144]
101521812  LAMTOR1; ragulator complex protein LAMTOR1 [KO:K20397]
101517408  ragulator complex protein LAMTOR2-like isoform X2 [KO:K20398]
101518311  LAMTOR2; ragulator complex protein LAMTOR2 isoform X1 [KO:K20398]
101533522  LAMTOR3; ragulator complex protein LAMTOR3 [KO:K04370]
101523934  LAMTOR4; ragulator complex protein LAMTOR4 [KO:K20399]
101520323  LAMTOR5; ragulator complex protein LAMTOR5 [KO:K16344]
118757855  ragulator complex protein LAMTOR5-like [KO:K16344]
101527359  FLCN; folliculin [KO:K09594]
101521148  FNIP1; folliculin-interacting protein 1 isoform X1 [KO:K20400]
101531829  FNIP2; folliculin-interacting protein 2 isoform X3 [KO:K20401]
101524595  RRAGB; ras-related GTP-binding protein B isoform X1 [KO:K16185]
101530273  RRAGA; ras-related GTP-binding protein A [KO:K16185]
101524499  RRAGC; ras-related GTP-binding protein C isoform X1 [KO:K16186]
101535092  RRAGD; ras-related GTP-binding protein D [KO:K16186]
101530551  SESN2; sestrin-2 [KO:K20394]
101521090  CASTOR1; cytosolic arginine sensor for mTORC1 subunit 1 [KO:K23080]
101525193  CASTOR2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
101518052  MIOS; GATOR complex protein MIOS isoform X1 [KO:K20407]
101534292  SEH1L; nucleoporin SEH1 [KO:K14299]
101535199  LOW QUALITY PROTEIN: GATOR complex protein WDR24-like [KO:K20408]
101534666  WDR24; GATOR complex protein WDR24 [KO:K20408]
101521798  WDR59; GATOR complex protein WDR59 [KO:K20409]
101531077  SEC13; protein SEC13 homolog [KO:K14004]
101528077  DEPDC5; LOW QUALITY PROTEIN: GATOR complex protein DEPDC5 [KO:K20404]
101534046  NPRL2; GATOR complex protein NPRL2 [KO:K20405]
101531470  NPRL3; GATOR complex protein NPRL3 [KO:K20406]
101531086  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
101518042  RNF152; E3 ubiquitin-protein ligase RNF152 [KO:K15705] [EC:2.3.2.27]
101536034  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
101519220  AKT1S1; proline-rich AKT1 substrate 1 [KO:K16184]
101525384  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101516486  DEPTOR; DEP domain-containing mTOR-interacting protein isoform X1 [KO:K20402]
101531258  MLST8; target of rapamycin complex subunit LST8 isoform X2 [KO:K08266]
101518975  TELO2; LOW QUALITY PROTEIN: telomere length regulation protein TEL2 homolog [KO:K11137]
101534229  TTI1; TELO2-interacting protein 1 homolog [KO:K20403]
101518334  CLIP1; CAP-Gly domain-containing linker protein 1 isoform X1 [KO:K10421]
101533322  GRB10; growth factor receptor-bound protein 10 isoform X1 [KO:K20064]
101535195  LPIN1; phosphatidate phosphatase LPIN1 [KO:K15728] [EC:3.1.3.4]
101516111  LPIN3; phosphatidate phosphatase LPIN3 [KO:K15728] [EC:3.1.3.4]
101519989  LPIN2; phosphatidate phosphatase LPIN2 [KO:K15728] [EC:3.1.3.4]
101521994  ULK1; serine/threonine-protein kinase ULK1 isoform X2 [KO:K21357] [EC:2.7.11.1]
101536556  ULK2; serine/threonine-protein kinase ULK2 [KO:K08269] [EC:2.7.11.1]
101532982  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101520923  EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259]
101518184  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
101528599  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E type 1B-like [KO:K03259]
101524098  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
101526118  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101528246  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101523190  EIF4B; eukaryotic translation initiation factor 4B [KO:K03258]
101529521  RPS6; 40S ribosomal protein S6 [KO:K02991]
101531933  STRADA; STE20-related kinase adapter protein alpha isoform X1 [KO:K08271]
101521353  STRADB; STE20-related kinase adapter protein beta isoform X1 [KO:K17532]
101531468  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
101521432  CAB39; calcium-binding protein 39 [KO:K08272]
101518675  CAB39L; calcium-binding protein 39-like [KO:K08272]
101536083  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
101525509  serine/threonine protein kinase OSK1-like [KO:K07198] [EC:2.7.11.31]
101529543  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
101520687  TSC1; hamartin [KO:K07206]
101519464  TSC2; tuberin isoform X2 [KO:K07207]
101525562  TBC1 domain family member 7 isoform X2 [KO:K20396]
101535564  RHEB; GTP-binding protein Rheb [KO:K07208]
101522117  DDIT4; DNA damage-inducible transcript 4 protein [KO:K08270]
101526533  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101519545  WNT2; protein Wnt-2 [KO:K00182]
101535993  WNT2B; protein Wnt-2b [KO:K00182]
101531097  WNT3A; protein Wnt-3a [KO:K00312]
101519718  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101532229  WNT4; protein Wnt-4 [KO:K00408]
101533147  WNT5B; protein Wnt-5b [KO:K00444]
101526139  WNT5A; protein Wnt-5a [KO:K00444]
101518428  WNT6; protein Wnt-6 [KO:K00445]
101525411  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
101527317  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
101535038  WNT8A; protein Wnt-8a [KO:K00714]
101530831  WNT8B; protein Wnt-8b [KO:K00714]
101535462  WNT9A; protein Wnt-9a [KO:K01064]
101519468  WNT9B; protein Wnt-9b [KO:K01064]
101526780  WNT10B; protein Wnt-10b [KO:K01357]
101518185  WNT10A; protein Wnt-10a [KO:K01357]
101530628  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
101521646  WNT16; protein Wnt-16 [KO:K01558]
101528861  FZD1; frizzled-1 [KO:K02432]
101519819  FZD7; frizzled-7 [KO:K02432]
101520542  FZD2; frizzled-2 [KO:K02235]
101528374  FZD3; frizzled-3 [KO:K02329]
101518239  FZD4; frizzled-4 [KO:K02354]
101532093  FZD5; frizzled-5 [KO:K02375]
101517741  FZD8; frizzled-8 [KO:K02375]
101524151  FZD6; frizzled-6 [KO:K02376]
101519524  FZD9; frizzled-9 [KO:K02842]
101520287  FZD10; frizzled-10 [KO:K02842]
101517031  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
101517587  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
101522688  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
101528918  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101516456  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
101533693  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101525561  TNF; tumor necrosis factor isoform X2 [KO:K03156]
101530319  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101517015  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101533865  insulin isoform X2 [KO:K04526]
101526004  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
101530887  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
101535483  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
101531037  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
101534610  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101525349  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101531636  HRAS; GTPase HRas [KO:K02833]
101534080  KRAS; GTPase KRas isoform X1 [KO:K07827]
101524465  NRAS; GTPase NRas [KO:K07828]
101526188  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
101534290  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101533612  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105942099  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
101529486  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101530701  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101525427  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101518406  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
101516934  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
101533181  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
101522594  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
101526197  IRS1; insulin receptor substrate 1 [KO:K16172]
101532354  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101517982  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101528030  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101519449  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101533851  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101533024  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101529935  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
101528473  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101533296  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101519021  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101525801  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101536073  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101536446  MAPKAP1; target of rapamycin complex 2 subunit MAPKAP1 [KO:K20410]
101534542  RICTOR; rapamycin-insensitive companion of mTOR isoform X1 [KO:K08267]
101529547  PRR5; proline-rich protein 5 [KO:K20411]
101518544  PRR5L; proline-rich protein 5-like isoform X1 [KO:K20411]
101525255  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
101535305  transforming protein RhoA-like isoform X1 [KO:K04513]
101523549  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101523439  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101534827  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101526325  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
opi00561  Glycerolipid metabolism
opi04010  MAPK signaling pathway
opi04140  Autophagy - animal
opi04151  PI3K-Akt signaling pathway
opi04152  AMPK signaling pathway
opi04810  Regulation of actin cytoskeleton
opi04910  Insulin signaling pathway
KO pathway
ko04150   
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