KEGG   PATHWAY: rno04150
Entry
rno04150                    Pathway                                
Name
mTOR signaling pathway - Rattus norvegicus (rat)
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
rno04150  mTOR signaling pathway
rno04150

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
50719  Slc7a5; large neutral amino acids transporter small subunit 1 [KO:K13780]
50567  Slc3a2; amino acid transporter heavy chain SLC3A2 isoform 2 [KO:K06519]
310091  Slc38a9; neutral amino acid transporter 9 [KO:K14995]
685232  Atp6v1a; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
117596  Atp6v1b2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
312488  Atp6v1b1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
299971  Atp6v1c1; V-type proton ATPase subunit C 1 [KO:K02148]
362802  Atp6v1c2; V-type proton ATPase subunit C 2 [KO:K02148]
299159  Atp6v1d; V-type proton ATPase subunit D [KO:K02149]
297566  Atp6v1e1; V-type proton ATPase subunit E 1 [KO:K02150]
366545  Atp6v1e2; V-type proton ATPase subunit E 2 [KO:K02150]
116664  Atp6v1f; V-type proton ATPase subunit F [KO:K02151]
289407  Atp6v1g3; V-type proton ATPase subunit G 3 [KO:K02152]
298103  Atp6v1g1; V-type proton ATPase subunit G 1 [KO:K02152]
368044  Atp6v1g2; V-type proton ATPase subunit G 2 [KO:K02152]
501686  Atp6v1g1l1; V-type proton ATPase subunit G 1-like [KO:K02152]
297797  Atp6v1h; V-type proton ATPase subunit H isoform 1 [KO:K02144]
100361543  Lamtor1l1; late endosomal/lysosomal adaptor, MAPK and MTOR activator 1 like 1 [KO:K20397]
308869  Lamtor1; ragulator complex protein LAMTOR1 [KO:K20397]
295234  Lamtor2; ragulator complex protein LAMTOR2 [KO:K20398]
362045  Lamtor3; ragulator complex protein LAMTOR3 [KO:K04370]
360776  Lamtor4; ragulator complex protein LAMTOR4 [KO:K20399]
295357  Lamtor5; ragulator complex protein LAMTOR5 [KO:K16344]
303185  Flcn; folliculin [KO:K09594]
100362347  Fnip1; folliculin-interacting protein 1 [KO:K20400]
310538  Fnip2; folliculin-interacting protein 2 [KO:K20401]
117044  Rraga; ras-related GTP-binding protein A [KO:K16185]
117043  RragB; ras-related GTP-binding protein B [KO:K16185]
297960  Rragd; ras-related GTP-binding protein D [KO:K16186]
298514  Rragc; ras-related GTP-binding protein C [KO:K16186]
502988  Sesn2; sestrin-2 [KO:K20394]
360969  Castor1; cytosolic arginine sensor for mTORC1 subunit 1 [KO:K23080]
304410  Castor2; cytosolic arginine sensor for mTORC1 subunit 2 [KO:K23081]
362324  Mios; GATOR complex protein MIOS [KO:K20407]
100911798  Seh1l; nucleoporin SEH1 [KO:K14299]
360497  Wdr24; GATOR complex protein WDR24 [KO:K20408]
690751  Wdr59; GATOR2 complex protein WDR59 isoform X1 [KO:K20409]
297522  Sec13; protein SEC13 homolog [KO:K14004]
305464  Depdc5; GATOR complex protein DEPDC5 [KO:K20404]
363138  Nprl2; GATOR complex protein NPRL2 [KO:K20405]
360505  Nprl3; GATOR complex protein NPRL3 isoform 1 [KO:K20406]
294790  Skp2; S-phase kinase-associated protein 2 [KO:K03875]
293561  Rnf152; E3 ubiquitin-protein ligase RNF152 [KO:K15705] [EC:2.3.2.27]
287871  Rptor; regulatory-associated protein of mTOR [KO:K07204]
292887  Akt1s1; proline-rich AKT1 substrate 1 [KO:K16184]
56718  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
314979  Deptor; DEP domain containing MTOR-interacting protein [KO:K20402]
64226  Mlst8; target of rapamycin complex subunit LST8 [KO:K08266]
302986  Telo2; telomere length regulation protein TEL2 homolog [KO:K11137]
499935  Tti1; TELO2-interacting protein 1 homolog [KO:K20403]
65201  Clip1; CAP-Gly domain-containing linker protein 1 isoform 1 [KO:K10421]
313977  Lpin1; phosphatidate phosphatase LPIN1 [KO:K15728] [EC:3.1.3.4]
362261  Lpin3; phosphatidate phosphatase LPIN3 [KO:K15728] [EC:3.1.3.4]
316737  Lpin2; phosphatidate phosphatase LPIN2 [KO:K15728] [EC:3.1.3.4]
360827  Ulk1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
303206  Ulk2; serine/threonine-protein kinase ULK2 [KO:K08269] [EC:2.7.11.1]
116636  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
117045  Eif4e; eukaryotic translation initiation factor 4E [KO:K03259]
686104  Eif4e1b; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
363275  Eif4e2; eukaryotic translation initiation factor 4E type 2 isoform 1 [KO:K03259]
83840  Rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
361696  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
300253  Eif4b; eukaryotic translation initiation factor 4B [KO:K03258]
29304  Rps6; small ribosomal subunit protein eS6 [KO:K02991]
303605  Strada; STE20-related kinase adapter protein alpha isoform 2 [KO:K08271]
501146  Stradb; STE20-related kinase adapter protein beta [KO:K17532]
314621  Stk11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
301574  Cab39; calcium-binding protein 39 isoform 1 [KO:K08272]
290291  Cab39l; calcium-binding protein 39-like [KO:K08272]
65248  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
78975  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
60445  Tsc1; hamartin [KO:K07206]
24855  Tsc2; tuberin [KO:K07207]
361227  Tbc1d7; TBC1 domain family member 7 [KO:K20396]
26954  Rheb; GTP-binding protein Rheb [KO:K07208]
140942  Ddit4; DNA damage-inducible transcript 4 protein [KO:K08270]
24881  Wnt1; proto-oncogene Wnt-1 precursor [KO:K03209]
116466  Wnt2b; protein Wnt-2b [KO:K00182]
114487  Wnt2; protein Wnt-2 precursor [KO:K00182]
24882  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
303181  Wnt3a; protein Wnt-3a precursor [KO:K00312]
84426  Wnt4; protein Wnt-4 precursor [KO:K00408]
64566  Wnt5a; protein Wnt-5a precursor [KO:K00444]
282582  Wnt5b; protein Wnt-5b precursor [KO:K00444]
316526  Wnt6; protein Wnt-6 precursor [KO:K00445]
114850  Wnt7a; protein Wnt-7a precursor [KO:K00572]
315196  Wnt7b; protein Wnt-7b isoform 1 [KO:K00572]
291678  Wnt8a; protein Wnt-8a precursor [KO:K00714]
293990  Wnt8b; protein Wnt-8b precursor [KO:K00714]
287357  Wnt9a; protein Wnt-9a precursor [KO:K01064]
303586  Wnt9b; protein Wnt-9b precursor [KO:K01064]
315294  Wnt10b; protein Wnt-10b precursor [KO:K01357]
316527  Wnt10a; protein Wnt-10a precursor [KO:K01357]
140584  Wnt11; protein Wnt-11 [KO:K01384]
500047  Wnt16; protein Wnt-16 precursor [KO:K01558]
58868  Fzd1; frizzled-1 precursor [KO:K02432]
100360552  Fzd7; frizzled-7 precursor [KO:K02432]
64512  Fzd2; frizzled-2 precursor [KO:K02235]
266715  Fzd3; frizzled-3 precursor [KO:K02329]
64558  Fzd4; frizzled-4 precursor [KO:K02354]
317674  Fzd5; frizzled-5 precursor [KO:K02375]
364754  Fzd8; frizzled-8 precursor [KO:K02375]
282581  Fzd6; frizzled-6 precursor [KO:K02376]
266608  Fzd9; frizzled-9 precursor [KO:K02842]
363913  Fzd10; frizzled-10 precursor [KO:K02842]
293649  Lrp5; low-density lipoprotein receptor-related protein 5 precursor [KO:K03068]
312781  Lrp6; low-density lipoprotein receptor-related protein 6 isoform 2 precursor [KO:K03068]
83721  Dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
303811  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
303251  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
24835  Tnf; tumor necrosis factor [KO:K03156]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
24506  Ins2; insulin-2 preproprotein [KO:K04526]
24505  Ins1; insulin-1 preproprotein [KO:K04526]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
24954  Insr; insulin receptor preproprotein [KO:K04527] [EC:2.7.10.1]
25718  Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087] [EC:2.7.10.1]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
114486  Braf; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
81771  Rps6ka1; ribosomal protein S6 kinase alpha-1 [KO:K04373] [EC:2.7.11.1]
117269  Rps6ka2; ribosomal protein S6 kinase alpha-2 [KO:K04373] [EC:2.7.11.1]
501560  Rps6ka3; ribosomal protein S6 kinase alpha-3 [KO:K04373] [EC:2.7.11.1]
317203  Rps6ka6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
25467  Irs1; insulin receptor substrate 1 [KO:K16172]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
50557  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]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
296648  Mapkap1; target of rapamycin complex 2 subunit MAPKAP1 [KO:K20410]
310131  Rictor; rapamycin-insensitive companion of mTOR isoform X3 [KO:K08267]
315189  Prr5; proline-rich protein 5 [KO:K20411]
362171  Prr5l; proline-rich protein 5-like [KO:K20411]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
29517  Sgk1; serine/threonine-protein kinase Sgk1 isoform 1 [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
rno00561  Glycerolipid metabolism
rno04010  MAPK signaling pathway
rno04140  Autophagy - animal
rno04151  PI3K-Akt signaling pathway
rno04152  AMPK signaling pathway
rno04810  Regulation of actin cytoskeleton
rno04910  Insulin signaling pathway
KO pathway
ko04150   
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