KEGG   PATHWAY: ko04150Help
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
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
ko04150  mTOR signaling pathway
ko04150

Ortholog table
Disease
H00666  Peutz-Jeghers syndrome
H00896  Lymphangioleiomyomatosis (LAM)
H00915  Tuberous sclerosis complex (TSC)
H01112  Polyhydramnios, megalencephaly, and symptomatic epilepsy
H01251  Focal cortical dysplasia of Taylor
H01691  Renal angiomyolipoma
H01692  Subependymal giant cell astrocytoma (SEGA)
H01885  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH)
H01909  Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH)
H01912  Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi
H01928  Smith-Kingsmore syndrome
H02111  Autism
H02153  Megalencephaly-capillary malformation syndrome
Orthology
K13780  solute carrier family 7 (L-type amino acid transporter), member 5
K06519  solute carrier family 3, member 2
K14995  solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 9
K02145  V-type H+-transporting ATPase subunit A [EC:3.6.3.14]
K02147  V-type H+-transporting ATPase subunit B
K02148  V-type H+-transporting ATPase subunit C
K02149  V-type H+-transporting ATPase subunit D
K02150  V-type H+-transporting ATPase subunit E
K02151  V-type H+-transporting ATPase subunit F
K02152  V-type H+-transporting ATPase subunit G
K02144  V-type H+-transporting ATPase subunit H
K20397  ragulator complex protein LAMTOR1
K20398  ragulator complex protein LAMTOR2
K04370  ragulator complex protein LAMTOR3
K20399  ragulator complex protein LAMTOR4
K16344  ragulator complex protein LAMTOR5
K09594  folliculin
K20400  folliculin-interacting protein 1
K20401  folliculin-interacting protein 2
K16185  Ras-related GTP-binding protein A/B
K16186  Ras-related GTP-binding protein C/D
K07204  regulatory associated protein of mTOR
K16184  proline-rich AKT1 substrate 1
K07203  serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K20402  DEP domain-containing mTOR-interacting protein
K08266  target of rapamycin complex subunit LST8
K11137  telomere length regulation protein
K20403  TELO2-interacting protein 1
K10421  CAP-Gly domain-containing linker protein 1
K20064  growth factor receptor-bound protein 10
K21357  serine/threonine-protein kinase ULK1 [EC:2.7.11.1]
K08269  serine/threonine-protein kinase ULK2 [EC:2.7.11.1]
K07205  eukaryotic translation initiation factor 4E binding protein 1
K03259  translation initiation factor 4E
K04688  ribosomal protein S6 kinase beta [EC:2.7.11.1]
K03258  translation initiation factor 4B
K02991  small subunit ribosomal protein S6e
K15705  E3 ubiquitin-protein ligase RNF152 [EC:2.3.2.27]
K03875  F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2)
K20404  DEP domain-containing protein 5
K20405  nitrogen permease regulator 2-like protein
K20406  nitrogen permease regulator 3-like protein
K20407  WD repeat-containing protein mio
K14299  nucleoporin SEH1
K20408  WD repeat-containing protein 24
K20409  WD repeat-containing protein 59
K14004  protein transport protein SEC13
K20394  sestrin 2
K08271  STE20-related kinase adapter protein alpha
K17532  STE20-related kinase adapter protein beta
K07298  serine/threonine-protein kinase 11 [EC:2.7.11.1]
K08272  calcium binding protein 39
K07198  5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.11]
K07206  tuberous sclerosis 1
K07207  tuberous sclerosis 2
K20396  TBC1 domain family member 7
K07208  Ras homolog enriched in brain
K08270  DNA-damage-inducible transcript 4
K03209  wingless-type MMTV integration site family, member 1
K00182  wingless-type MMTV integration site family, member 2
K00312  wingless-type MMTV integration site family, member 3
K00408  wingless-type MMTV integration site family, member 4
K00444  wingless-type MMTV integration site family, member 5
K00445  wingless-type MMTV integration site family, member 6
K00572  wingless-type MMTV integration site family, member 7
K00714  wingless-type MMTV integration site family, member 8
K01064  wingless-type MMTV integration site family, member 9
K01357  wingless-type MMTV integration site family, member 10
K01384  wingless-type MMTV integration site family, member 11
K01558  wingless-type MMTV integration site family, member 16
K02432  frizzled 1/7
K02235  frizzled 2
K02329  frizzled 3
K02354  frizzled 4
K02375  frizzled 5/8
K02376  frizzled 6
K02842  frizzled 9/10
K04690  frizzled
K03068  low density lipoprotein receptor-related protein 5/6
K02353  segment polarity protein dishevelled
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03156  tumor necrosis factor superfamily, member 2
K03158  tumor necrosis factor receptor superfamily member 1A
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K04526  insulin
K05459  insulin-like growth factor 1
K04527  insulin receptor [EC:2.7.10.1]
K05087  insulin-like growth factor 1 receptor [EC:2.7.10.1]
K04364  growth factor receptor-binding protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04373  ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1]
K16172  insulin receptor substrate 1
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01110  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.67 3.1.3.48 3.1.3.16]
K06276  3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K20410  target of rapamycin complex 2 subunit MAPKAP1
K08267  rapamycin-insensitive companion of mTOR
K20411  proline-rich protein 5
K04513  Ras homolog gene family, member A
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K13302  serum/glucocorticoid-regulated kinase 1 [EC:2.7.11.1]
Compound
C00020  AMP
C00123  L-Leucine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
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