KEGG   PATHWAY: acyg04910
Entry
acyg04910                   Pathway                                
Name
Insulin signaling pathway - Anser cygnoides (swan goose)
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
acyg04910  Insulin signaling pathway
acyg04910

Organism
Anser cygnoides (swan goose) [GN:acyg]
Gene
106042601  INS; insulin [KO:K04526]
106044962  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
106036186  IRS1; insulin receptor substrate 1 [KO:K16172]
106038523  IRS4; insulin receptor substrate 4 [KO:K07187]
106044455  IRS2; insulin receptor substrate 2 [KO:K07187]
106033049  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
106042106  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
106045000  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
106032026  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106044285  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
106040311  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
106046039  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X2 [KO:K06276] [EC:2.7.11.1]
106049522  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
106037213  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106049631  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106037022  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
106038297  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
136788644  LOW QUALITY PROTEIN: glycogen [starch] synthase, muscle-like [KO:K00693] [EC:2.4.1.11]
136789315  LOW QUALITY PROTEIN: glycogen [starch] synthase, muscle-like [KO:K00693] [EC:2.4.1.11]
106031410  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
106029776  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
125180844  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
106046100  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
106040819  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
106042960  PPP1R3C; protein phosphatase 1 regulatory subunit 3C isoform X2 [KO:K07189]
106042060  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
106033162  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
136786272  protein phosphatase 1 regulatory subunit 3C-B-like isoform X2 [KO:K07189]
106041427  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
106037817  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
106049532  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
106039581  PHKB; phosphorylase b kinase regulatory subunit beta isoform X5 [KO:K07190]
106043683  CALML4; calmodulin-like protein 4 [KO:K02183]
106038708  calmodulin, striated muscle [KO:K02183]
136787514  CALM3; calmodulin-3 [KO:K02183]
106029779  CALM2; calmodulin-2 [KO:K02183]
106036749  CALM1; calmodulin-1 [KO:K02183]
106049305  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
106044725  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
136788781  LOW QUALITY PROTEIN: glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
136789273  LOW QUALITY PROTEIN: glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
106040925  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
106034038  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
106035471  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
106034773  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
106042032  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit isoform X1 [KO:K04739]
106033526  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
106044643  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
106031987  PRKCI; protein kinase C iota type isoform X2 [KO:K06069] [EC:2.7.11.13]
106049420  FLOT2; flotillin-2 isoform X5 [KO:K07192]
125181343  FLOT1; flotillin-1 [KO:K07192]
106041497  SH2B2; SH2B adapter protein 2 [KO:K07193]
106029990  SORBS1; LOW QUALITY PROTEIN: sorbin and SH3 domain-containing protein 1 [KO:K06086]
106039784  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
106041393  CRK; adapter molecule crk isoform X1 [KO:K04438]
106031307  CRKL; crk-like protein [KO:K04438]
106044103  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
106048289  RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
106034627  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
125183049  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
106043774  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
106031086  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
106046771  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
106048916  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
106049507  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
106030903  hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
106030908  hexokinase HKDC1-like [KO:K00844] [EC:2.7.1.1]
125180994  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
106033088  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
106036363  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
106031361  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
106041622  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
106047717  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
106039315  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200]
106036828  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X8 [KO:K07200]
106035078  FOXO1; forkhead box protein O1 [KO:K07201]
106035743  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X2 [KO:K07202]
106048005  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
106029962  G6PC2; glucose-6-phosphatase 2 isoform X2 [KO:K01084] [EC:3.1.3.9]
106045365  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
106045370  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
106041991  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
125181711  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
136788786  phosphoenolpyruvate carboxykinase [GTP], mitochondrial-like isoform X1 [KO:K01596] [EC:4.1.1.32]
106040228  MTOR; serine/threonine-protein kinase mTOR isoform X3 [KO:K07203] [EC:2.7.11.1]
106046774  RPTOR; regulatory-associated protein of mTOR isoform X2 [KO:K07204]
125180835  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
106046854  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
106044160  RPS6; small ribosomal subunit protein eS6 [KO:K02991]
106044378  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
106044821  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X4 [KO:K03259]
106049504  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
106048946  EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259]
106044091  TSC1; hamartin isoform X1 [KO:K07206]
106032149  TSC2; tuberin isoform X1 [KO:K07207]
106036836  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
106048510  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
106049094  SHC2; SHC-transforming protein 2 [KO:K17447]
106045108  SHC3; SHC-transforming protein 3 isoform X2 [KO:K17448]
106033799  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
106034739  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
106049938  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
106045585  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
106031749  HRAS; GTPase HRas [KO:K02833]
106038277  KRAS; GTPase KRas isoform X1 [KO:K07827]
106041320  NRAS; GTPase NRas [KO:K07828]
106030997  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
106040056  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X4 [KO:K04366] [EC:2.7.11.1]
106043651  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
106044951  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106031260  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106033042  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
106045652  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K04372] [EC:2.7.11.1]
106041226  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
106046730  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
106044059  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
106041511  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
106034013  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
106041872  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
106047189  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
106032805  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
106044397  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
106042953  phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909] [EC:3.1.3.86]
125180051  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
106047331  INPP5A; 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
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
acyg00010  Glycolysis / Gluconeogenesis
acyg00061  Fatty acid biosynthesis
acyg00500  Starch and sucrose metabolism
acyg04010  MAPK signaling pathway
acyg04070  Phosphatidylinositol signaling system
acyg04210  Apoptosis
KO pathway
ko04910   
LinkDB

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