KEGG   PATHWAY: cjo04910
Entry
cjo04910                    Pathway                                
Name
Insulin signaling pathway - Coturnix japonica (Japanese quail)
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
cjo04910  Insulin signaling pathway
cjo04910

Organism
Coturnix japonica (Japanese quail) [GN:cjo]
Gene
107314531  INS; insulin [KO:K04526]
107325585  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
107318049  IRS1; insulin receptor substrate 1 [KO:K16172]
107307936  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
107312783  IRS4; insulin receptor substrate 4 [KO:K07187]
107317608  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107305909  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107325533  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
107317945  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
107318114  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107323497  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
107320588  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
107307290  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
107315293  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107311258  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107319718  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107316995  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
107314245  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
107311180  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
107321188  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
107322986  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
107309219  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
107315941  PPP1R3C; protein phosphatase 1 regulatory subunit 3C isoform X2 [KO:K07189]
107313499  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
116652397  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
107322445  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
107312519  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
107319241  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
107325369  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
107312134  calmodulin, striated muscle [KO:K02183]
107315214  CALM1; calmodulin-1 [KO:K02183]
107311165  CALM2; calmodulin-2 [KO:K02183]
107318948  CALML4; calmodulin-like protein 4 [KO:K02183]
107307130  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
107310736  glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
107315529  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
107314630  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
107317471  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107307213  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
107320721  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
107322219  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
107319781  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
107323428  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
107318323  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
107306987  solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
107307322  FLOT1; flotillin-1 [KO:K07192]
107322576  FLOT2; flotillin-2 isoform X1 [KO:K07192]
107322455  SH2B2; SH2B adapter protein 2 [KO:K07193]
107315825  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X23 [KO:K06086]
107324207  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
107321076  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
107321452  CRKL; crk-like protein [KO:K04438]
107322427  CRK; adapter molecule crk isoform X1 [KO:K04438]
107321760  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
107311158  RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
107322017  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
107320619  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
107322768  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
107321488  ACACB; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
107322058  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
107315732  HK1; hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
107315745  hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
107323647  hexokinase-2 [KO:K00844] [EC:2.7.1.1]
107320403  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
107323664  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
107305860  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
107317703  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
107317110  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
107321393  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
107308766  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
107317021  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
107325757  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
107308196  FOXO1; forkhead box protein O1 [KO:K07201]
107314036  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
107316743  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
107325229  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
107325302  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
107306278  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
107306279  fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
107307214  phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
107323226  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
107323407  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
107322223  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
107314239  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
107322434  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
107306170  RPS6; 40S ribosomal protein S6 [KO:K02991]
107323781  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
107318242  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
107313667  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
107320493  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
107321823  TSC1; hamartin isoform X1 [KO:K07206]
107320601  TSC2; tuberin isoform X1 [KO:K07207]
107308769  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
107324486  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
107325668  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
107306293  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
107318783  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
107322339  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107315513  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
107310899  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107314494  HRAS; GTPase HRas isoform X1 [KO:K02833]
107317023  KRAS; GTPase KRas isoform X1 [KO:K07827]
107324818  NRAS; GTPase NRas [KO:K07828]
107315883  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
107319673  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
107318921  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107325595  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107321038  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107317624  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
107325341  MKNK2; LOW QUALITY PROTEIN: MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
107320828  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
107311591  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
107322171  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
107315453  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
107323063  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
107317429  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X2 [KO:K05695] [EC:3.1.3.48]
107313439  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
107315851  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
107320159  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107323740  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
107312645  phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2-like isoform X1 [KO:K15909] [EC:3.1.3.86]
107316265  INPP5A; inositol polyphosphate-5-phosphatase A isoform X2 [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
PMID:14635525
  Authors
Ogawa W, Kasuga M.
  Title
[Mechanism of insulin action and diabetes mellitus]
  Journal
Seikagaku 75:1332-44 (2003)
Reference
PMID:11282018
  Authors
Bevan P.
  Title
Insulin signalling.
  Journal
J Cell Sci 114:1429-30 (2001)
Reference
PMID:12867054
  Authors
Kanzaki M, Pessin JE.
  Title
Insulin signaling: GLUT4 vesicles exit via the exocyst.
  Journal
Curr Biol 13:R574-6 (2003)
DOI:10.1016/S0960-9822(03)00478-0
Reference
PMID:10196204
  Authors
Moodie SA, Alleman-Sposeto J, Gustafson TA.
  Title
Identification of the APS protein as a novel insulin receptor substrate.
  Journal
J Biol Chem 274:11186-93 (1999)
DOI:10.1074/jbc.274.16.11186
Reference
PMID:15733744
  Authors
Gual P, Le Marchand-Brustel Y, Tanti JF.
  Title
Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.
  Journal
Biochimie 87:99-109 (2005)
DOI:10.1016/j.biochi.2004.10.019
Reference
PMID:9748166
  Authors
Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P, Parker PJ.
  Title
Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1.
  Journal
Science 281:2042-5 (1998)
DOI:10.1126/science.281.5385.2042
Reference
PMID:11742412
  Authors
Saltiel AR, Kahn CR.
  Title
Insulin signalling and the regulation of glucose and lipid metabolism.
  Journal
Nature 414:799-806 (2001)
DOI:10.1038/414799a
Reference
PMID:15624019
  Authors
Inoki K, Corradetti MN, Guan KL.
  Title
Dysregulation of the TSC-mTOR pathway in human disease.
  Journal
Nat Genet 37:19-24 (2005)
DOI:10.1038/ng1494
Reference
PMID:16288289
  Authors
Ruggero D, Sonenberg N.
  Title
The Akt of translational control.
  Journal
Oncogene 24:7426-34 (2005)
DOI:10.1038/sj.onc.1209098
Reference
PMID:10567225
  Authors
Nave BT, Ouwens M, Withers DJ, Alessi DR, Shepherd PR.
  Title
Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.
  Journal
Biochem J 344 Pt 2:427-31 (1999)
DOI:10.1042/bj3440427
Reference
PMID:9445476
  Authors
Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G.
  Title
Phosphorylation and activation of p70s6k by PDK1.
  Journal
Science 279:707-10 (1998)
DOI:10.1126/science.279.5351.707
Reference
PMID:9609110
  Authors
Ogawa W, Matozaki T, Kasuga M.
  Title
Role of binding proteins to IRS-1 in insulin signalling.
  Journal
Mol Cell Biochem 182:13-22 (1998)
Reference
PMID:9609111
  Authors
Ceresa BP, Pessin JE.
  Title
Insulin regulation of the Ras activation/inactivation cycle.
  Journal
Mol Cell Biochem 182:23-9 (1998)
Reference
PMID:15229476
  Authors
Pollak MN, Schernhammer ES, Hankinson SE.
  Title
Insulin-like growth factors and neoplasia.
  Journal
Nat Rev Cancer 4:505-18 (2004)
DOI:10.1038/nrc1387
Reference
PMID:9346240
  Authors
Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME.
  Title
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.
  Journal
Cell 91:231-41 (1997)
DOI:10.1016/S0092-8674(00)80405-5
Reference
PMID:17344645
  Authors
Ferre P, Foufelle F
  Title
SREBP-1c transcription factor and lipid homeostasis: clinical perspective.
  Journal
Horm Res 68:72-82 (2007)
DOI:10.1159/000100426
Reference
PMID:18291668
  Authors
Raghow R, Yellaturu C, Deng X, Park EA, Elam MB
  Title
SREBPs: the crossroads of physiological and pathological lipid homeostasis.
  Journal
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
cjo00010  Glycolysis / Gluconeogenesis
cjo00061  Fatty acid biosynthesis
cjo00500  Starch and sucrose metabolism
cjo04010  MAPK signaling pathway
cjo04070  Phosphatidylinositol signaling system
cjo04210  Apoptosis
KO pathway
ko04910   
LinkDB

DBGET integrated database retrieval system