KEGG   PATHWAY: otc04910
Entry
otc04910                    Pathway                                
Name
Insulin signaling pathway - Onychostruthus taczanowskii (white-rumped snowfinch)
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
otc04910  Insulin signaling pathway
otc04910

Organism
Onychostruthus taczanowskii (white-rumped snowfinch) [GN:otc]
Gene
121331431  PPP1R3B; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
121331759  IRS4; insulin receptor substrate 4 [KO:K07187]
121331787  [KO:K15909] [EC:3.1.3.86]
121332015  CALM1; calmodulin-1 [KO:K02183]
121332065  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
121332174  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
121332208  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121332354  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
121332416  HK3; hexokinase-3 [KO:K00844] [EC:2.7.1.1]
121332631  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121332732  SHC3; SHC-transforming protein 3 [KO:K17448]
121332742  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
121332765  KRAS; GTPase KRas [KO:K07827]
121333048  RPS6; 40S ribosomal protein S6 [KO:K02991]
121333278  [KO:K03841] [EC:3.1.3.11]
121333284  [KO:K03841] [EC:3.1.3.11]
121333481  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
121333629  INPP5A; inositol polyphosphate-5-phosphatase A isoform X1 [KO:K01106] [EC:3.1.3.56]
121333814  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
121333888  [KO:K07189]
121334108  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
121334168  [KO:K02183]
121334283  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
121334348  TSC2; tuberin isoform X1 [KO:K07207]
121334387  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
121334523  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
121334611  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
121334660  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
121334932  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
121335434  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
121335752  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121335754  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
121335781  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
121336047  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
121336330  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
121336528  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121336580  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
121336653  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
121336850  TSC1; hamartin isoform X1 [KO:K07206]
121336856  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
121337288  FOXO1; forkhead box protein O1 [KO:K07201]
121337870  FLOT1; flotillin-1 isoform X1 [KO:K07192]
121337953  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
121337985  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
121338244  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
121338247  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
121338255  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
121338287  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
121338296  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
121338493  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
121338675  SOS2; son of sevenless homolog 2 [KO:K03099]
121338832  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
121338872  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
121338915  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
121339021  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121339328  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
121339681  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
121339690  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
121339886  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121340629  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
121340632  CALM2; calmodulin-2 [KO:K02183]
121340671  RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
121340694  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
121340814  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
121341146  IRS1; insulin receptor substrate 1 [KO:K16172]
121341205  [KO:K00688] [EC:2.4.1.1]
121341222  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121341361  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
121341478  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
121341561  INS; insulin [KO:K04526]
121341581  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
121341643  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
121341824  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121341954  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
121342130  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
121342974  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
121343027  PTPN1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
121343042  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
121343099  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
121343474  SHC4; SHC-transforming protein 4 [KO:K17449]
121343488  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
121343563  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
121343885  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
121343951  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121344040  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
121344310  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
121344397  CRKL; crk-like protein [KO:K04438]
121344496  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
121344800  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
121344866  HRAS; GTPase HRas [KO:K02833]
121344945  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
121344962  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
121344995  [KO:K02649]
121345002  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
121345095  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
121345439  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
121345473  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
121345569  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
121345673  NRAS; GTPase NRas [KO:K07828]
121345696  CRK; adapter molecule crk isoform X1 [KO:K04438]
121345734  FLOT2; flotillin-2 isoform X1 [KO:K07192]
121345767  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
121345777  SH2B2; SH2B adapter protein 2 [KO:K07193]
121346340  [KO:K00688] [EC:2.4.1.1]
121346515  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
121346555  EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259]
121346662  [KO:K00844] [EC:2.7.1.1]
121346673  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
121346709  [KO:K07189]
121346775  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
121346776  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
121346813  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 isoform X1 [KO:K07205]
121346999  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
121347017  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
121347140  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
121347527  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
121347613  G6PC1; glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
121348091  [KO:K00844] [EC:2.7.1.1]
121348092  [KO:K00844] [EC:2.7.1.1]
121348231  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
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
otc00010  Glycolysis / Gluconeogenesis
otc00061  Fatty acid biosynthesis
otc00500  Starch and sucrose metabolism
otc04010  MAPK signaling pathway
otc04070  Phosphatidylinositol signaling system
otc04210  Apoptosis
KO pathway
ko04910   

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