KEGG   PATHWAY: gmu04910
Entry
gmu04910                    Pathway                                
Name
Insulin signaling pathway - Girardinichthys multiradiatus (darkedged splitfin)
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
gmu04910  Insulin signaling pathway
gmu04910

Organism
Girardinichthys multiradiatus (darkedged splitfin) [GN:gmu]
Gene
124860812  insb; preproinsulin b [KO:K04526]
124875874  ins; insulin isoform X1 [KO:K04526]
124869846  insra; insulin receptor a [KO:K04527] [EC:2.7.10.1]
124874283  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
124876829  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
124880703  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
124871251  irs2b; insulin receptor substrate 2 isoform X1 [KO:K07187]
124880406  insulin receptor substrate 2-A [KO:K07187]
124861643  insulin receptor substrate 2-like isoform X1 [KO:K07187]
124870480  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
124877742  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
124872596  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124873683  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
124873763  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
124869460  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124870477  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124884243  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124873577  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
124880409  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
124875686  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
124875685  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
124883780  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124858601  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124867765  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124855241  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124871205  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
124864053  glycogen [starch] synthase, muscle-like [KO:K00693] [EC:2.4.1.11]
124862302  glycogen [starch] synthase, muscle-like [KO:K00693] [EC:2.4.1.11]
124882709  gys2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
124862833  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
124855846  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
124864323  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
124877642  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
124880276  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
124875557  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
124883412  ppp1r3aa; uncharacterized protein ppp1r3aa [KO:K07189]
124856554  ppp1r3db; protein phosphatase 1, regulatory subunit 3Db [KO:K07189]
124870937  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
124877401  ppp1r3c2b; protein phosphatase 1 regulatory subunit 3C-B-like isoform X1 [KO:K07189]
124872148  ppp1r3b; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
124858911  ppp1r3cb; protein phosphatase 1 regulatory subunit 3C-B [KO:K07189]
124866896  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
124866975  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
124875108  protein phosphatase 1 regulatory subunit 3C-B-like isoform X1 [KO:K07189]
124884141  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform-like [KO:K00871] [EC:2.7.11.19]
124875028  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
124866600  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
124867036  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
124880718  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
124855816  calm1a; calmodulin-1a [KO:K02183]
124883886  calm3a; calmodulin 3a (phosphorylase kinase, delta) isoform X1 [KO:K02183]
124859157  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
124867418  calml4a; calmodulin-like protein 4a [KO:K02183]
124881816  calmodulin-1 [KO:K02183]
124855580  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
124876932  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
124880537  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
124866948  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
124862895  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
124870299  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
124864749  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124873964  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
124869187  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
124863574  cAMP-dependent protein kinase type I-beta regulatory subunit-like [KO:K04739]
124863744  cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
124871626  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
124881139  cAMP-dependent protein kinase type II-beta regulatory subunit isoform X1 [KO:K04739]
124875410  cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
124865649  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
124879454  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
124868029  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
124869597  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
124880686  solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
124876292  flotillin-2a isoform X1 [KO:K07192]
124883988  flotillin-2 isoform X1 [KO:K07192]
124863982  flot1b; flotillin-1b [KO:K07192]
124879675  flot1a; flotillin-1a [KO:K07192]
124884355  SH2B adapter protein 2 [KO:K07193]
124859571  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
124876272  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
124883956  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
124876940  adapter molecule crk-like [KO:K04438]
124884098  crk; adapter molecule crk [KO:K04438]
124872914  crkl; crk-like protein isoform X1 [KO:K04438]
124877125  rap guanine nucleotide exchange factor 1-like [KO:K06277]
124872361  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X1 [KO:K06277]
124858996  rhoq; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
124874999  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
124862734  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
124864813  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
124868644  cdc42-interacting protein 4 homolog [KO:K07196]
124862694  sterol regulatory element-binding protein 1-like [KO:K07197]
124864368  sterol regulatory element-binding protein 1-like [KO:K07197]
124876262  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
124877619  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
124875110  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
124877936  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
124866714  hexokinase HKDC1-like [KO:K00844] [EC:2.7.1.1]
124866715  hexokinase-1-like [KO:K00844] [EC:2.7.1.1]
124868311  hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
124875821  hexokinase-2-like [KO:K00844] [EC:2.7.1.1]
124878136  gck; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
124872711  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
124873586  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
124877269  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
124872782  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a isoform X1 [KO:K07199]
124869932  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
124871092  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b [KO:K07200]
124857371  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
124857837  5'-AMP-activated protein kinase subunit gamma-2-like [KO:K07200]
124861372  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
124883726  foxo1a; forkhead box protein O1-A [KO:K07201]
124875925  forkhead box protein O1-A-like [KO:K07201]
124880702  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
124871660  glucose-6-phosphatase 2-like isoform X1 [KO:K01084] [EC:3.1.3.9]
124874840  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
124874856  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
124875607  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
124878021  fbp1a; fructose-1,6-bisphosphatase 1a [KO:K03841] [EC:3.1.3.11]
124878150  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
124872733  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
124856982  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
124858081  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
124867337  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
124868207  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
124876390  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
124884239  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
124868300  ribosomal protein S6 kinase beta-2-like isoform X1 [KO:K04688] [EC:2.7.11.1]
124868485  rps6; 40S ribosomal protein S6 [KO:K02991]
124877350  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
124872717  eukaryotic translation initiation factor 4E-binding protein 1-like isoform X1 [KO:K07205]
124855574  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
124869872  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
124858644  eif4e1c; eukaryotic translation initiation factor 4E family member 1c isoform X1 [KO:K03259]
124859786  eif4ea; eukaryotic translation initiation factor 4E-1A [KO:K03259]
124877475  tsc1a; TSC complex subunit 1a isoform X1 [KO:K07206]
124872672  tsc1b; TSC complex subunit 1b isoform X1 [KO:K07206]
124867678  tsc2; tuberin isoform X1 [KO:K07207]
124856495  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
124870639  GTP-binding protein Rheb [KO:K07208]
124857988  rheb; GTP-binding protein Rheb isoform X1 [KO:K07208]
124880840  badb; BCL2 associated agonist of cell death b [KO:K02158]
124865598  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
124874121  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
124872742  shc3; SHC-transforming protein 3 [KO:K17448]
124867254  SHC-transforming protein 4-like [KO:K17449]
124863357  growth factor receptor-bound protein 2 [KO:K04364]
124863971  growth factor receptor-bound protein 2 [KO:K04364]
124868143  son of sevenless homolog 1-like isoform X1 [KO:K03099]
124855236  sos2; son of sevenless homolog 2 [KO:K03099]
124882413  GTPase HRas [KO:K02833]
124863530  GTPase KRas-like isoform X1 [KO:K07827]
124864335  GTPase KRas-like isoform X1 [KO:K07827]
124879131  kras; GTPase KRas isoform X1 [KO:K07827]
124878222  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
124883025  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
124866030  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
124856513  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124874089  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
124863274  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
124864295  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
124877799  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124873971  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
124874316  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
124868529  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
124863120  suppressor of cytokine signaling 1-like [KO:K04694]
124864623  suppressor of cytokine signaling 1-like [KO:K04694]
124868645  suppressor of cytokine signaling 1-like [KO:K04694]
124882834  socs2; suppressor of cytokine signaling 2 [KO:K04695]
124864481  suppressor of cytokine signaling 3-like isoform X1 [KO:K04696]
124862195  suppressor of cytokine signaling 3-like [KO:K04696]
124875219  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
124867350  socs4; suppressor of cytokine signaling 4 [KO:K04697]
124858472  ptpn1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
124870025  ptprfb; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
124873491  ptprfa; protein tyrosine phosphatase receptor type Fa [KO:K05695] [EC:3.1.3.48]
124872468  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
124859135  mapk8a; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
124860150  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
124875307  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
124877211  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
124883607  inppl1a; LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
124860385  inppl1b; inositol polyphosphate phosphatase-like 1b [KO:K15909] [EC:3.1.3.86]
124858855  inositol polyphosphate-5-phosphatase A-like isoform X1 [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
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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Reference
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Reference
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DOI:10.1016/j.tem.2007.10.009
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
gmu00010  Glycolysis / Gluconeogenesis
gmu00061  Fatty acid biosynthesis
gmu00500  Starch and sucrose metabolism
gmu04010  MAPK signaling pathway
gmu04070  Phosphatidylinositol signaling system
gmu04210  Apoptosis
KO pathway
ko04910   
LinkDB

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