KEGG   PATHWAY: stow04910
Entry
stow04910                   Pathway                                
Name
Insulin signaling pathway - Sphaerodactylus townsendi (Townsend's least gecko)
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
stow04910  Insulin signaling pathway
stow04910

Organism
Sphaerodactylus townsendi (Townsend's least gecko) [GN:stow]
Gene
125426313  insulin-like [KO:K04526]
125426951  INS; insulin [KO:K04526]
125432863  INSR; LOW QUALITY PROTEIN: insulin receptor [KO:K04527] [EC:2.7.10.1]
125437863  IRS1; insulin receptor substrate 1 [KO:K16172]
125444504  insulin receptor substrate 1-like [KO:K16172]
125442689  IRS4; insulin receptor substrate 4 [KO:K07187]
125426447  LOW QUALITY PROTEIN: insulin receptor substrate 2-like [KO:K07187]
125437816  LOW QUALITY PROTEIN: insulin receptor substrate 2-like [KO:K07187]
125436164  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125432754  phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
125433242  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
125445925  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125437957  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125438330  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125444496  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
125431736  PDPK1; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
125426629  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125426854  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125436058  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125434315  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
125444989  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
125441803  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
125442686  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
125425980  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
125441504  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
125435590  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
125436778  PPP1R3B; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
125443703  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
125432460  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
125438295  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
125445132  PPP1R3E; protein phosphatase 1 regulatory subunit 3E [KO:K07189]
125427661  PPP1R3F; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 3F [KO:K17453]
125444796  PHKG2; LOW QUALITY PROTEIN: phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
125445464  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
125431142  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
125442798  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
125443824  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
125445790  CALML6; calmodulin-like protein 6 [KO:K02183]
125445828  calmodulin-like protein 4 [KO:K02183]
125435432  calmodulin-A-like [KO:K02183]
125435433  calmodulin-like [KO:K02183]
125441638  calmodulin-alpha isoform X1 [KO:K02183]
125425089  CALM2; calmodulin-2 [KO:K02183]
125426638  CALM1; calmodulin-1 [KO:K02183]
125446086  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
125442744  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
125426429  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
125425778  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
125428187  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
125432825  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125434300  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
125428494  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
125429049  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
125431117  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
125435512  LIPE; LOW QUALITY PROTEIN: hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
125445667  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
125437920  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
125445158  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191]
125445655  FLOT2; flotillin-2 isoform X1 [KO:K07192]
125429082  FLOT1; flotillin-1 isoform X1 [KO:K07192]
125445449  SH2B2; SH2B adapter protein 2 [KO:K07193]
125437862  SORBS1; sorbin and SH3 domain-containing protein 1 [KO:K06086]
125441931  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
125435516  CBLC; E3 ubiquitin-protein ligase CBL-C [KO:K22517] [EC:2.3.2.27]
125431059  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
125444894  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL-B-like [KO:K22517] [EC:2.3.2.27]
125445863  CRK; adapter molecule crk isoform X1 [KO:K04438]
125442799  CRKL; crk-like protein isoform X1 [KO:K04438]
125444678  crk-like protein [KO:K04438]
125441665  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
125425145  RHOQ; rho-related GTP-binding protein RhoQ [KO:K07194]
125427850  EXOC7; exocyst complex component 7 [KO:K07195]
125429481  TRIP10; LOW QUALITY PROTEIN: cdc42-interacting protein 4 [KO:K07196]
125431176  SREBF1; sterol regulatory element-binding protein 1 [KO:K07197]
125425223  ACACA; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125442513  ACACB; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125428348  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
125436554  pyruvate kinase PKM-like [KO:K12406] [EC:2.7.1.40]
125441829  hexokinase-2-like isoform X1 [KO:K00844] [EC:2.7.1.1]
125437545  hexokinase HKDC1-like isoform X1 [KO:K00844] [EC:2.7.1.1]
125427802  HK3; hexokinase-3 [KO:K00844] [EC:2.7.1.1]
125442282  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
125436509  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
125432803  PRKAA2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
125434038  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
125443170  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
125428996  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
125440506  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
125426530  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
125434363  FOXO1; forkhead box protein O1 [KO:K07201]
125439828  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
125426218  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
125443727  glucose-6-phosphatase catalytic subunit 1-like [KO:K01084] [EC:3.1.3.9]
125443728  glucose-6-phosphatase catalytic subunit 1-like [KO:K01084] [EC:3.1.3.9]
125445331  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
125436040  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
125437219  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
125433038  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
125445188  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
125445584  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
125428401  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
125445502  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
125426142  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
125436490  RPS6; 40S ribosomal protein S6 [KO:K02991]
125442096  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
125428265  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
125439902  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
125438164  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
125441757  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
125431771  TSC2; tuberin isoform X1 [KO:K07207]
125440912  RHEB; GTP-binding protein Rheb [KO:K07208]
125441612  BAD; bcl2-associated agonist of cell death [KO:K02158]
125440647  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
125433261  SHC2; SHC-transforming protein 2 [KO:K17447]
125436789  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
125429172  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
125424526  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
125427095  SOS2; son of sevenless homolog 2 [KO:K03099]
125426937  HRAS; GTPase HRas [KO:K02833]
125434327  KRAS; GTPase KRas isoform X1 [KO:K07827]
125444900  GTPase HRas-like [KO:K07827]
125433511  NRAS; GTPase NRas [KO:K07828]
125429274  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
125434335  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
125429531  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125432678  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125444669  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125432613  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
125432970  MKNK2; LOW QUALITY PROTEIN: MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
125427982  ELK1; LOW QUALITY PROTEIN: ETS domain-containing protein Elk-1 [KO:K04375]
125430499  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
125434765  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
125430269  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
125445263  suppressor of cytokine signaling 3-like [KO:K04696]
125427025  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
125432957  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
125432929  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
125440222  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125437878  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125427657  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125441474  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
125430834  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909] [EC:3.1.3.86]
125437730  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
stow00010  Glycolysis / Gluconeogenesis
stow00061  Fatty acid biosynthesis
stow00500  Starch and sucrose metabolism
stow04010  MAPK signaling pathway
stow04070  Phosphatidylinositol signaling system
stow04210  Apoptosis
KO pathway
ko04910   
LinkDB

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