KEGG   PATHWAY: tros04910
Entry
tros04910                   Pathway                                
Name
Insulin signaling pathway - Triplophysa rosa
Description
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR.
Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. SHC is another substrate of INSR. When tyrosine phosphorylated, SHC associates with GRB2 and can thus activate the RAS/MAPK pathway independently of IRS-1.
Class
Organismal Systems; Endocrine system
Pathway map
tros04910  Insulin signaling pathway
tros04910

Organism
Triplophysa rosa [GN:tros]
Gene
130561055  insulin [KO:K04526]
130549556  ins; insulin [KO:K04526]
130554143  insra; insulin receptor a [KO:K04527] [EC:2.7.10.1]
130549201  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
130564634  irs1; insulin receptor substrate 1-B [KO:K16172]
130570466  irs4a; insulin receptor substrate 2-B [KO:K07187]
130555712  irs2b; insulin receptor substrate 2 [KO:K07187]
130551433  insulin receptor substrate 2-B [KO:K07187]
130555087  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
130566832  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
130556269  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
130545256  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
130545271  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
130564405  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
130570982  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
130547188  pdpk1b; 3-phosphoinositide dependent protein kinase 1b [KO:K06276] [EC:2.7.11.1]
130562084  pdpk1a; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1a [KO:K06276] [EC:2.7.11.1]
130546009  akt2l; v-akt murine thymoma viral oncogene homolog 2, like [KO:K04456] [EC:2.7.11.1]
130553513  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
130559416  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
130565792  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
130560557  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
130562835  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
130553417  gsk3bb; glycogen synthase kinase 3 beta, genome duplicate b [KO:K03083] [EC:2.7.11.26]
130556037  gsk3ba; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
130547997  gys2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
130562125  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
130545463  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit A-like [KO:K06269] [EC:3.1.3.16]
130559154  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
130559873  ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
130561682  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
130568937  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
130552190  ppp1r3ab; uncharacterized protein ppp1r3ab [KO:K07189]
130570442  ppp1r3b; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
130571042  ppp1r3db; protein phosphatase 1, regulatory subunit 3Db [KO:K07189]
130571819  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
130560597  ppp1r3ca; protein phosphatase 1, regulatory subunit 3Ca [KO:K07189]
130568291  si:ch211-167b20.8; uncharacterized protein si:ch211-167b20.8 isoform X1 [KO:K07189]
130568428  ppp1r3c2b; protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
130550311  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
130569128  ppp1r3cb; protein phosphatase 1 regulatory subunit 3C-B [KO:K07189]
130569472  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
130565281  phkg1a; phosphorylase kinase, gamma 1a (muscle) isoform X1 [KO:K00871] [EC:2.7.11.19]
130571201  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
130561769  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
130557434  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
130552055  calml4b; calmodulin-like protein 4 [KO:K02183]
130570339  calm3b; calmodulin 3b (phosphorylase kinase, delta) [KO:K02183]
130564955  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
130553341  calml4a; calmodulin-like protein 4a isoform X1 [KO:K02183]
130559215  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
130560137  calm1a; calmodulin-1a [KO:K02183]
130550509  calmodulin-1 [KO:K02183]
130568830  calm2b; calmodulin 2b, (phosphorylase kinase, delta) isoform X1 [KO:K02183]
130570194  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
130559122  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
130559694  pygmb; phosphorylase, glycogen, muscle b [KO:K00688] [EC:2.4.1.1]
130560056  pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
130564311  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
130553214  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
130554282  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
130571504  prkacba; protein kinase, cAMP-dependent, catalytic, beta a [KO:K04345] [EC:2.7.11.11]
130561020  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a [KO:K04345] [EC:2.7.11.11]
130551581  cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
130569362  prkar1ab; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) b [KO:K04739]
130548546  prkar2ab; protein kinase, cAMP-dependent, regulatory, type II, alpha, B [KO:K04739]
130561516  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
130567860  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
130562190  prkar1aa; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) a [KO:K04739]
130567264  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
130557543  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
130568638  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
130553854  prkci; LOW QUALITY PROTEIN: protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
130554156  solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
130558469  flot1b; flotillin-1b [KO:K07192]
130564635  flot2b; flotillin-2b [KO:K07192]
130566645  flot1a; flotillin-1a [KO:K07192]
130568477  flot2a; flotillin-2a isoform X1 [KO:K07192]
130565015  SH2B adapter protein 2 [KO:K07193]
130558700  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
130564410  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
130545654  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
130564632  crk; adapter molecule crk [KO:K04438]
130570638  crkl; crk-like protein [KO:K04438]
130570093  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X1 [KO:K06277]
130568193  rapgef1a; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
130568829  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
130568914  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
130561584  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
130561340  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
130565482  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
130565610  acacb; LOW QUALITY PROTEIN: acetyl-CoA carboxylase [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
130568943  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
130558884  hkdc1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
130558885  hk1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
130568615  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
130567946  gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
130565660  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
130566724  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
130546487  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a isoform X1 [KO:K07199]
130549572  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
130568661  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b isoform X1 [KO:K07199]
130553409  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
130553895  prkag2b; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
130547358  prkag2a; 5'-AMP-activated protein kinase subunit gamma-2a isoform X1 [KO:K07200]
130555524  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b isoform X1 [KO:K07200]
130557030  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
130564689  foxo1a; forkhead box protein O1-A [KO:K07201]
130546124  foxo1b; forkhead box protein O1-B [KO:K07201]
130554932  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
130569300  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
130569557  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
130569210  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
130569543  fbp1a; fructose-1,6-bisphosphatase 1a [KO:K03841] [EC:3.1.3.11]
130546630  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
130572027  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
130547219  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
130556883  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
130567611  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
130556605  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
130569611  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
130564643  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
130545839  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
130553521  rps6; 40S ribosomal protein S6 [KO:K02991]
130569695  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
130563928  eif4ea; eukaryotic translation initiation factor 4E-1A [KO:K03259]
130545584  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 [KO:K03259]
130559014  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
130546621  eif4e1b; eukaryotic translation initiation factor 4E-1B isoform X1 [KO:K03259]
130559591  eif4e1c; eukaryotic translation initiation factor 4E family member 1c isoform X1 [KO:K03259]
130555055  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
130570278  tsc1b; TSC complex subunit 1b [KO:K07206]
130546551  tsc1a; LOW QUALITY PROTEIN: TSC complex subunit 1a [KO:K07206]
130553344  tsc2; tuberin [KO:K07207]
130549642  rheb; GTP-binding protein Rheb [KO:K07208]
130569788  bada; bcl2-associated agonist of cell death [KO:K02158]
130556339  badb; BCL2 associated agonist of cell death b [KO:K02158]
130557460  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
130548718  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
130570122  shc3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
130561572  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
130559547  sos2; son of sevenless homolog 2 [KO:K03099]
130571463  sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
130551615  hrasa; HRas proto-oncogene, GTPase a [KO:K02833]
130554426  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
130551760  kras; GTPase KRas [KO:K07827]
130561674  zgc:55558; GTPase KRas [KO:K07827]
130567677  nras; GTPase NRas [KO:K07828]
130565845  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
130547780  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
130570996  raf1b; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
130562953  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
130553870  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
130549161  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
130564406  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
130561543  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
130554101  mknk2a; LOW QUALITY PROTEIN: MAP kinase-interacting serine/threonine-protein kinase 2a [KO:K04372] [EC:2.7.11.1]
130571682  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
130568010  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
130567935  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
130553160  socs1b; suppressor of cytokine signaling 1b isoform X1 [KO:K04694]
130561579  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
130547760  socs2; suppressor of cytokine signaling 2 [KO:K04695]
130569602  socs3b; LOW QUALITY PROTEIN: suppressor of cytokine signaling 3b [KO:K04696]
130562217  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
130560666  socs4; suppressor of cytokine signaling 4 [KO:K04697]
130568305  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
130553991  ptprfb; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
130556751  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
130569911  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
130569997  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
130558723  mapk8a; LOW QUALITY PROTEIN: mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
130567729  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
130564066  inppl1b; inositol polyphosphate phosphatase-like 1b isoform X1 [KO:K15909] [EC:3.1.3.86]
130550876  inppl1a; LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
Compound
C00031  D-Glucose
C00369  Starch
C00575  3',5'-Cyclic AMP
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
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Reference
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Phosphorylation and activation of p70s6k by PDK1.
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Reference
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Role of binding proteins to IRS-1 in insulin signalling.
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Reference
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Insulin regulation of the Ras activation/inactivation cycle.
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Reference
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Insulin-like growth factors and neoplasia.
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Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.
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Reference
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SREBPs: the crossroads of physiological and pathological lipid homeostasis.
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Reference
PMID:11343120
  Authors
Clement S, Krause U, Desmedt F, Tanti JF, Behrends J, Pesesse X, Sasaki T, Penninger J, Doherty M, Malaisse W, Dumont JE, Le Marchand-Brustel Y, Erneux C, Hue L, Schurmans S
  Title
The lipid phosphatase SHIP2 controls insulin sensitivity.
  Journal
Nature 409:92-7 (2001)
DOI:10.1038/35051094
Reference
PMID:12791379
  Authors
Backers K, Blero D, Paternotte N, Zhang J, Erneux C
  Title
The termination of PI3K signalling by SHIP1 and SHIP2 inositol 5-phosphatases.
  Journal
Adv Enzyme Regul 43:15-28 (2003)
DOI:10.1016/S0065-2571(02)00043-2
Related
pathway
tros00010  Glycolysis / Gluconeogenesis
tros00061  Fatty acid biosynthesis
tros00500  Starch and sucrose metabolism
tros04010  MAPK signaling pathway
tros04070  Phosphatidylinositol signaling system
tros04210  Apoptosis
KO pathway
ko04910   
LinkDB

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