KEGG   PATHWAY: els04910
Entry
els04910                    Pathway                                
Name
Insulin signaling pathway - Esox lucius (northern pike)
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
els04910  Insulin signaling pathway
els04910

Organism
Esox lucius (northern pike) [GN:els]
Gene
105025960  insulin [KO:K04526]
105021727  insulin [KO:K04526]
105005877  insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
105022623  insulin receptor [KO:K04527] [EC:2.7.10.1]
105020633  insulin receptor substrate 1-B isoform X1 [KO:K16172]
105023953  insulin receptor substrate 1-B [KO:K16172]
105009026  insulin receptor substrate 2 [KO:K07187]
105030862  insulin receptor substrate 2-B-like [KO:K07187]
105016500  irs2; insulin receptor substrate 2 [KO:K07187]
105024652  insulin receptor substrate 2-A-like [KO:K07187]
105024545  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105026229  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105015144  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105021974  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109614581  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
105025378  phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
105026926  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105025897  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105028918  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105009929  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
105029118  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
105021296  pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
105023568  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105017614  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105015651  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105024916  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105021234  akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105021541  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105027876  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105031009  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105007707  glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
105020183  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
105012949  serine/threonine-protein phosphatase alpha-2 isoform [KO:K06269] [EC:3.1.3.16]
105020693  serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
105024808  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
105014191  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
105024386  serine/threonine-protein phosphatase alpha-2 isoform isoform X1 [KO:K06269] [EC:3.1.3.16]
105006638  protein phosphatase 1 regulatory subunit 3D [KO:K07189]
105014714  ppp1r3b; protein phosphatase 1 regulatory subunit 3B isoform X3 [KO:K07189]
105018629  FK506-binding protein 5 isoform X1 [KO:K07189]
105022983  protein phosphatase 1 regulatory subunit 3D-like isoform X1 [KO:K07189]
105026656  ppp1r3a; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
105027283  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
105022407  uncharacterized protein LOC105022407 isoform X1 [KO:K07189]
105025134  ppp1r3c; protein phosphatase 1 regulatory subunit 3C isoform X1 [KO:K07189]
114828917  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
105021305  phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
105030287  phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
105007262  phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
105019913  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
105026361  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
105030792  calm2; calmodulin [KO:K02183]
105015473  calm1; calmodulin [KO:K02183]
105012083  calm3; calmodulin-3 [KO:K02183]
114839877  rab11 family-interacting protein 4A-like [KO:K02183]
105013934  calmodulin-like protein 4 [KO:K02183]
105017693  calmodulin [KO:K02183]
105025440  calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105018659  calmodulin-like protein 4 isoform X2 [KO:K02183]
105028068  calmodulin [KO:K02183]
105010907  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
105025547  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
105020707  pygm; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
105025522  pygb; glycogen phosphorylase, brain form isoform X1 [KO:K00688] [EC:2.4.1.1]
105022265  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
105013090  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105008738  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105029732  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105019307  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105012797  cAMP-dependent protein kinase type I-alpha regulatory subunit isoform X1 [KO:K04739]
105005679  prkar1a; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
105021651  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
105025266  prkar2a; cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X1 [KO:K04739]
105029719  cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
105016848  slc25a20; mitochondrial carnitine/acylcarnitine carrier protein isoform X1 [KO:K04739]
105025658  cAMP-dependent protein kinase type II-beta regulatory subunit-like isoform X1 [KO:K04739]
105024275  lipe; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
105027558  hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
105028269  hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
105023788  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
105022740  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
105020675  slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
105011286  flotillin-2 isoform X1 [KO:K07192]
105019225  flotillin-1 [KO:K07192]
105030985  flot2; flotillin-2 isoform X1 [KO:K07192]
105028591  flotillin-1 [KO:K07192]
105011112  SH2B adapter protein 2 [KO:K07193]
105005599  sh2b2; SH2B adapter protein 2 isoform X3 [KO:K07193]
105028653  sorbs1; sorbin and SH3 domain-containing protein 1 [KO:K06086]
105011087  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
105012434  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
105028781  cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
105005921  adapter molecule crk [KO:K04438]
105015072  crkl; crk-like protein [KO:K04438]
105024111  adapter molecule crk [KO:K04438]
105014664  rapgef1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
105028395  rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
105010713  rhoq; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
105027404  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
105027469  cdc42-interacting protein 4 homolog isoform X2 [KO:K07196]
105028441  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
105013003  srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
105010777  acaca; acetyl-CoA carboxylase 1 isoform X4 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
105014434  acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
105021150  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
105014353  hexokinase-2 [KO:K00844] [EC:2.7.1.1]
105021332  putative hexokinase HKDC1 isoform X1 [KO:K00844] [EC:2.7.1.1]
105021333  hk1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
105021496  hexokinase-1 [KO:K00844] [EC:2.7.1.1]
105014407  gck; glucokinase [KO:K12407] [EC:2.7.1.2]
105015246  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
105011784  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
105020860  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
105014960  5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
105014211  5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
105027313  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
105018996  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
105017212  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
105027970  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
105023716  5'-AMP-activated protein kinase subunit gamma-3-like isoform X1 [KO:K07200]
105007737  forkhead box protein O1-A [KO:K07201]
105008116  foxo1; forkhead box protein O1 [KO:K07201]
105022109  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
105007052  glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
105007579  glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
105007595  g6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
105021182  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
105027923  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
105030215  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
105030214  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
105019502  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
105030571  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
105013925  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
105021612  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
105010995  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
105022224  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
105030187  rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
105030947  rps6; 40S ribosomal protein S6 [KO:K02991]
105027007  eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
105007409  eukaryotic translation initiation factor 4E type 2 [KO:K03259]
105010873  eukaryotic translation initiation factor 4E-1B isoform X1 [KO:K03259]
105010612  eukaryotic translation initiation factor 4E-like isoform X1 [KO:K03259]
105020966  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X2 [KO:K03259]
105027498  eukaryotic translation initiation factor 4E-1A isoform X1 [KO:K03259]
105023310  eukaryotic translation initiation factor 4E-1A isoform X1 [KO:K03259]
105027820  hamartin isoform X1 [KO:K07206]
105024185  tsc1; hamartin isoform X1 [KO:K07206]
105031540  tsc2; tuberin isoform X1 [KO:K07207]
105025720  rheb; GTP-binding protein Rheb [KO:K07208]
105030778  GTP-binding protein Rheb [KO:K07208]
105017211  rhebl1; GTPase RhebL1 [KO:K07208]
114839466  bad; bcl2-associated agonist of cell death [KO:K02158]
105024470  shc1; SHC-transforming protein 1 isoform X2 [KO:K06279]
105011583  shc2; SHC-transforming protein 2 isoform X2 [KO:K17447]
105031363  shc3; SHC-transforming protein 3 isoform X2 [KO:K17448]
105012273  growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105013161  growth factor receptor-bound protein 2 [KO:K04364]
105025539  sos2; son of sevenless homolog 2 [KO:K03099]
105026828  son of sevenless homolog 1 isoform X3 [KO:K03099]
105018344  hras; GTPase HRas [KO:K02833]
105022136  kras; GTPase KRas isoform X1 [KO:K07827]
105029053  GTPase HRas-like [KO:K07827]
105014388  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105006078  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105013076  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
105029139  RAF proto-oncogene serine/threonine-protein kinase-like isoform X1 [KO:K04366] [EC:2.7.11.1]
105006978  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105011557  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105020581  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
105012809  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105006515  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105006075  MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
105028139  MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
105011671  mknk2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
105006467  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
105007127  socs1; suppressor of cytokine signaling 1 [KO:K04694]
105009400  suppressor of cytokine signaling 1 isoform X1 [KO:K04694]
105027835  socs2; suppressor of cytokine signaling 2 [KO:K04695]
105013055  suppressor of cytokine signaling 3 [KO:K04696]
105021322  suppressor of cytokine signaling 3 [KO:K04696]
105023278  suppressor of cytokine signaling 4 [KO:K04697]
105022331  tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
105011872  ptprf; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
105022906  receptor-type tyrosine-protein phosphatase F isoform X8 [KO:K05695] [EC:3.1.3.48]
105006595  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105031053  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105024911  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
105025816  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105027233  mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
105014298  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105029605  inppl1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
105010721  inpp5a; type I inositol 1,4,5-trisphosphate 5-phosphatase isoform X1 [KO:K01106] [EC:3.1.3.56]
105014248  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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Trends Endocrinol Metab 19:65-73 (2008)
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
els00010  Glycolysis / Gluconeogenesis
els00061  Fatty acid biosynthesis
els00500  Starch and sucrose metabolism
els04010  MAPK signaling pathway
els04070  Phosphatidylinositol signaling system
els04210  Apoptosis
KO pathway
ko04910   
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