KEGG   PATHWAY: aoce04910
Entry
aoce04910                   Pathway                                
Name
Insulin signaling pathway - Amphiprion ocellaris (clown anemonefish)
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
aoce04910  Insulin signaling pathway
aoce04910

Organism
Amphiprion ocellaris (clown anemonefish) [GN:aoce]
Gene
111588046  LOW QUALITY PROTEIN: insulin-like [KO:K04526]
111587296  ins; insulin [KO:K04526]
111566177  insulin-like [KO:K04526]
111565521  insr; insulin receptor [KO:K04527] [EC:2.7.10.1]
111569056  insulin receptor-like [KO:K04527] [EC:2.7.10.1]
111571694  insulin receptor substrate 1-B-like [KO:K16172]
111566540  insulin receptor substrate 2-like isoform X1 [KO:K07187]
111566595  irs2; insulin receptor substrate 2 [KO:K07187]
111580299  insulin receptor substrate 1-B-like [KO:K07187]
111575407  insulin receptor substrate 2-B-like [KO:K07187]
111566849  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111573943  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
111569137  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
111586970  phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
111566758  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
111582380  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111587052  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
111573373  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111586024  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
111588464  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
111569702  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111581473  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111584920  pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
111584424  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
111570511  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111581166  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111581655  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
111566093  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111578103  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111565339  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
111573502  gys2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
111582709  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
111567166  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
111573267  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
111578332  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
111587839  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
111568695  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
111565210  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
111563347  ppp1r3a; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
111566408  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
111586176  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
111588355  protein phosphatase 1 regulatory subunit 3A-like isoform X1 [KO:K07189]
111579531  intracellular protein transport protein USO1-like [KO:K07189]
111582573  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
111588674  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
111585287  ppp1r3c; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
111568817  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
111572299  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
111564740  phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
111584911  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
111565762  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
111567333  phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
111562726  phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
111579918  calml6; calmodulin-like protein 6 [KO:K02183]
111574006  calm2; calmodulin-2 [KO:K02183]
111568350  calml4; calmodulin-like protein 4 [KO:K02183]
111585476  calm1; calmodulin-1 [KO:K02183]
111566088  calmodulin [KO:K02183]
111582363  calmodulin isoform X1 [KO:K02183]
111584579  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
111587492  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
111567108  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
111563275  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
111573654  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
111577932  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
111586379  cAMP-dependent protein kinase catalytic subunit beta-like [KO:K04345] [EC:2.7.11.11]
111579002  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111562596  cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
111574647  prkar2b; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
111576891  cAMP-dependent protein kinase type II-alpha regulatory subunit-like [KO:K04739]
111570013  cAMP-dependent protein kinase type II-alpha regulatory subunit-like [KO:K04739]
111574377  cAMP-dependent protein kinase type II-alpha regulatory subunit-like [KO:K04739]
111578316  prkar1a; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
111564221  lipe; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
111580224  hormone-sensitive lipase-like [KO:K07188] [EC:3.1.1.79]
111572559  protein kinase C zeta type-like isoform X1 [KO:K18952] [EC:2.7.11.13]
111565532  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
111577182  slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
111565391  flotillin-1 [KO:K07192]
111569454  flot1; flotillin-1 [KO:K07192]
111572708  flotillin-2a isoform X1 [KO:K07192]
111575183  flotillin-2a-like [KO:K07192]
111579408  flotillin-2-like [KO:K07192]
111575972  sh2b2; SH2B adapter protein 2 [KO:K07193]
111573102  sorbs1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
111582911  sorbs2; sorbin and SH3 domain-containing protein 2 isoform X1 [KO:K06086]
111587912  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
111586006  E3 ubiquitin-protein ligase CBL-like isoform X1 [KO:K04707] [EC:2.3.2.27]
111567948  E3 ubiquitin-protein ligase CBL-B-like isoform X1 [KO:K22517] [EC:2.3.2.27]
111562712  adapter molecule crk-like [KO:K04438]
111575126  adapter molecule crk-like [KO:K04438]
111578832  crkl; crk-like protein [KO:K04438]
111564078  rapgef1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
111586833  rap guanine nucleotide exchange factor 1-like isoform X1 [KO:K06277]
111573989  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
111585256  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
111574817  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
111566259  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
111578189  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
111571760  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
111568287  acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
111564925  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
111571320  glucokinase-like isoform X1 [KO:K00844] [EC:2.7.1.1]
111576917  hexokinase-2-like [KO:K00844] [EC:2.7.1.1]
111576190  putative hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
111576191  hexokinase-1-like [KO:K00844] [EC:2.7.1.1]
111581369  hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
111567820  gck; glucokinase [KO:K12407] [EC:2.7.1.2]
111574778  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
111579210  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
111586174  5'-AMP-activated protein kinase subunit beta-1-like [KO:K07199]
111574312  5'-AMP-activated protein kinase subunit beta-1-like [KO:K07199]
111567643  5'-AMP-activated protein kinase subunit beta-2-like [KO:K07199]
111568751  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
111588686  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
111566618  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
111570138  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
111575261  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
111563615  forkhead box protein O1-A-like [KO:K07201]
111588523  forkhead box protein O1-A-like [KO:K07201]
111573584  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
111572823  g6pc2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
111568614  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
111568511  glucose-6-phosphatase-like [KO:K01084] [EC:3.1.3.9]
111568514  g6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
111565426  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
111570715  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
111570716  fructose-1,6-bisphosphatase isozyme 2-like isoform X1 [KO:K03841] [EC:3.1.3.11]
111566859  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
111579341  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
111567358  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
111567444  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
111588930  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
111566696  rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
111579842  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
111579520  rps6; 40S ribosomal protein S6 [KO:K02991]
111565730  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
111575825  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
111564366  eukaryotic translation initiation factor 4E-like [KO:K03259]
111562576  eif4e; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259]
111586027  eukaryotic translation initiation factor 4E type 2-like [KO:K03259]
111588375  eukaryotic translation initiation factor 4E-1A-like [KO:K03259]
111567652  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
111567968  hamartin-like [KO:K07206]
111571907  tsc2; tuberin isoform X1 [KO:K07207]
111581436  GTP-binding protein Rheb-like [KO:K07208]
111566628  GTP-binding protein Rheb-like [KO:K07208]
111576980  GTP-binding protein Rheb isoform X1 [KO:K07208]
111588385  bad; bcl2-associated agonist of cell death [KO:K02158]
111566077  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
111573492  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
111585351  shc3; SHC-transforming protein 3 isoform X1 [KO:K17448]
111565759  shc4; SHC-transforming protein 4 isoform X1 [KO:K17449]
111567912  grb2; growth factor receptor-bound protein 2 [KO:K04364]
111579378  sos2; son of sevenless homolog 2 [KO:K03099]
111563950  sos1; son of sevenless homolog 1 [KO:K03099]
111584369  hras; GTPase HRas [KO:K02833]
111565328  GTPase HRas-like [KO:K07827]
111563125  kras; GTPase KRas isoform X1 [KO:K07827]
111568015  serine/threonine-protein kinase A-Raf-like [KO:K08845] [EC:2.7.11.1]
111573494  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111588716  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111573164  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111568133  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111572311  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
111565366  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
111578326  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111580179  mknk2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
111581923  MAP kinase-interacting serine/threonine-protein kinase 1-like [KO:K04372] [EC:2.7.11.1]
111569157  suppressor of cytokine signaling 1-like [KO:K04694]
111583346  suppressor of cytokine signaling 1-like [KO:K04694]
111586987  suppressor of cytokine signaling 2-like [KO:K04695]
111581361  suppressor of cytokine signaling 2-like [KO:K04695]
111564669  socs3; suppressor of cytokine signaling 3 [KO:K04696]
111582347  suppressor of cytokine signaling 3-like [KO:K04696]
111575116  socs4; suppressor of cytokine signaling 4 [KO:K04697]
111572074  tyrosine-protein phosphatase non-receptor type 1-like [KO:K05696] [EC:3.1.3.48]
111575489  receptor-type tyrosine-protein phosphatase F [KO:K05695] [EC:3.1.3.48]
111573927  receptor-type tyrosine-protein phosphatase F-like [KO:K05695] [EC:3.1.3.48]
111588767  ptprf; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
111575648  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111577431  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
111569535  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
111582355  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
111577292  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
111579643  phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2B-like isoform X1 [KO:K15909] [EC:3.1.3.86]
111570870  inppl1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
111582154  type I inositol 1,4,5-trisphosphate 5-phosphatase-like [KO:K01106] [EC:3.1.3.56]
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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Reference
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Reference
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Science 279:707-10 (1998)
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Reference
PMID:9609110
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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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Reference
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Reference
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Reference
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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
aoce00010  Glycolysis / Gluconeogenesis
aoce00061  Fatty acid biosynthesis
aoce00500  Starch and sucrose metabolism
aoce04010  MAPK signaling pathway
aoce04070  Phosphatidylinositol signaling system
aoce04210  Apoptosis
KO pathway
ko04910   
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