KEGG   PATHWAY: schu04910
Entry
schu04910                   Pathway                                
Name
Insulin signaling pathway - Siniperca chuatsi (mandarin fish)
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
schu04910  Insulin signaling pathway
schu04910

Organism
Siniperca chuatsi (mandarin fish) [GN:schu]
Gene
122888298  ins; insulin [KO:K04526]
122880879  insb; preproinsulin b [KO:K04526]
122887603  insra; insulin receptor a isoform X1 [KO:K04527] [EC:2.7.10.1]
122878004  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
122888843  si:ch211-284e13.4; insulin receptor substrate 1-B isoform X1 [KO:K16172]
122870633  si:ch73-335l21.1; insulin receptor substrate 1-B isoform X1 [KO:K16172]
122869974  insulin receptor substrate 2-B isoform X1 [KO:K07187]
122872245  insulin receptor substrate 2-like isoform X1 [KO:K07187]
122885444  irs2b; insulin receptor substrate 2 isoform X1 [KO:K07187]
122887535  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
122876770  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
122877580  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
122878127  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
122865334  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122887224  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122870088  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
122883224  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122878181  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
122878474  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122886592  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122868056  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
122888423  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
122878451  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122884935  akt3a; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122873144  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122861346  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122885418  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
122871183  gys2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
122862044  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like isoform X1 [KO:K06269] [EC:3.1.3.16]
122868775  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
122877056  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
122863717  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like isoform X1 [KO:K06269] [EC:3.1.3.16]
122870617  serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
122867951  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
122876198  ppp1r3c2b; protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
122882463  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
122883147  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
122871148  ppp1r3aa; uncharacterized protein ppp1r3aa isoform X1 [KO:K07189]
122884345  ppp1r3cb; protein phosphatase 1 regulatory subunit 3C-B [KO:K07189]
122865306  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
122873899  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
122867321  protein phosphatase 1 regulatory subunit 3C-B-like isoform X1 [KO:K07189]
122878820  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform-like isoform X1 [KO:K00871] [EC:2.7.11.19]
122868074  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
122875371  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
122875708  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
122870056  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
122863352  calm1b; calmodulin-1b [KO:K02183]
122884956  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
122885282  calglandulin-like [KO:K02183]
122879636  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
122873955  calml4a; calmodulin-like protein 4a [KO:K02183]
122874568  calml4b; calmodulin-like protein 4 isoform X1 [KO:K02183]
122861589  calm1a; calmodulin-1a [KO:K02183]
122888660  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
122870772  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
122884265  pygb; LOW QUALITY PROTEIN: glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
122861452  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
122873253  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
122868669  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
122877466  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
122873333  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
122887397  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
122868812  cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
122882477  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
122869566  prkar1aa; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) a isoform X1 [KO:K04739]
122868124  cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
122881968  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
122864997  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
122882939  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
122887609  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
122870058  solute carrier family 2, facilitated glucose transporter member 4-like isoform X1 [KO:K07191]
122882048  flot1b; flotillin-1b isoform X1 [KO:K07192]
122888446  flotillin-2a isoform X1 [KO:K07192]
122864428  flot1a; flotillin-1a isoform X1 [KO:K07192]
122879626  flotillin-2 [KO:K07192]
122879674  SH2B adapter protein 2 [KO:K07193]
122884847  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
122887977  E3 ubiquitin-protein ligase CBL-like isoform X1 [KO:K04707] [EC:2.3.2.27]
122879350  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
122888420  cblb; E3 ubiquitin-protein ligase CBL-B-B isoform X1 [KO:K22517] [EC:2.3.2.27]
122887817  adapter molecule crk-like [KO:K04438]
122878707  crk; adapter molecule crk [KO:K04438]
122866117  crkl; crk-like protein [KO:K04438]
122875993  LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1-like [KO:K06277]
122865682  rapgef1b; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1b [KO:K06277]
122884943  rho-related GTP-binding protein RhoQ [KO:K07194]
122867229  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
122868571  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
122870812  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
122868579  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
122888060  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
122876475  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
122867158  fasn; fatty acid synthase isoform X1 [KO:K00665] [EC:2.3.1.85]
122887719  hexokinase-2-like isoform X1 [KO:K00844] [EC:2.7.1.1]
122876026  hkdc1; hexokinase HKDC1 isoform X1 [KO:K00844] [EC:2.7.1.1]
122876032  hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
122876207  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
122872855  hexokinase-1-like isoform X1 [KO:K00844] [EC:2.7.1.1]
122876290  gck; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
122877156  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
122866157  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
122876033  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
122865732  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
122886406  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
122872181  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
122885372  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b [KO:K07200]
122867091  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
122887133  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
122888851  forkhead box protein O1-A-like isoform X1 [KO:K07201]
122878567  foxo1a; forkhead box protein O1-A [KO:K07201]
122870028  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
122885851  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
122867147  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
122867323  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
122867324  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
122876101  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
122876104  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
122865951  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
122863401  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
122866816  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
122883280  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122872748  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
122888190  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122878761  rps6kb1b; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122873242  ribosomal protein S6 kinase beta-2-like isoform X1 [KO:K04688] [EC:2.7.11.1]
122873006  rps6; 40S ribosomal protein S6 [KO:K02991]
122876592  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
122865456  eukaryotic translation initiation factor 4E-binding protein 1-like isoform X1 [KO:K07205]
122870283  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 [KO:K03259]
122884080  eif4e1c; eukaryotic translation initiation factor 4E family member 1c isoform X1 [KO:K03259]
122879944  eukaryotic translation initiation factor 4E-1A-like [KO:K03259]
122886515  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
122861392  eif4eb; eukaryotic translation initiation factor 4eb isoform X1 [KO:K03259]
122876153  tsc1a; TSC complex subunit 1a [KO:K07206]
122865188  tsc1b; TSC complex subunit 1b isoform X1 [KO:K07206]
122873522  tsc2; tuberin isoform X1 [KO:K07207]
122872739  GTP-binding protein Rheb-like [KO:K07208]
122866506  GTP-binding protein Rheb-like [KO:K07208]
122867099  rhebl1; ras homolog, mTORC1 binding like 1 isoform X1 [KO:K07208]
122886563  rheb; GTP-binding protein Rheb isoform X1 [KO:K07208]
122869670  badb; BCL2 associated agonist of cell death b [KO:K02158]
122882185  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
122877343  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
122865784  shc3; SHC-transforming protein 3 [KO:K17448]
122873301  SHC-transforming protein 4-like isoform X1 [KO:K17449]
122869414  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
122862135  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
122872843  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
122875107  GTPase HRas [KO:K02833]
122874834  kras; GTPase KRas isoform X1 [KO:K07827]
122876305  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
122871272  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122883572  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
122875138  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
122877476  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
122886281  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
122876093  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122877654  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
122878064  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
122882657  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
122874065  socs1b; suppressor of cytokine signaling 1b [KO:K04694]
122871553  socs2; suppressor of cytokine signaling 2 [KO:K04695]
122868952  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
122867274  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
122886467  socs4; suppressor of cytokine signaling 4 [KO:K04697]
122883628  tyrosine-protein phosphatase non-receptor type 1-like [KO:K05696] [EC:3.1.3.48]
122878208  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
122886346  LOW QUALITY PROTEIN: receptor-type tyrosine-protein phosphatase F-like [KO:K05695] [EC:3.1.3.48]
122883942  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122865666  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122880393  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122867451  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122875692  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
122878891  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
122880414  inppl1b; inositol polyphosphate phosphatase-like 1b isoform X1 [KO:K15909] [EC:3.1.3.86]
122884277  inositol polyphosphate-5-phosphatase A 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
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Reference
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Reference
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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
schu00010  Glycolysis / Gluconeogenesis
schu00061  Fatty acid biosynthesis
schu00500  Starch and sucrose metabolism
schu04010  MAPK signaling pathway
schu04070  Phosphatidylinositol signaling system
schu04210  Apoptosis
KO pathway
ko04910   
LinkDB

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