KEGG   PATHWAY: sund04910
Entry
sund04910                   Pathway                                
Name
Insulin signaling pathway - Sceloporus undulatus (fence lizard)
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
sund04910  Insulin signaling pathway
sund04910

Organism
Sceloporus undulatus (fence lizard) [GN:sund]
Gene
121918950  INS; insulin [KO:K04526]
121916648  LOW QUALITY PROTEIN: insulin receptor-like [KO:K04527] [EC:2.7.10.1]
121934423  insulin receptor substrate 1-like isoform X1 [KO:K16172]
121925778  IRS1; insulin receptor substrate 1 [KO:K16172]
121919404  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
121936111  IRS4; insulin receptor substrate 4 [KO:K07187]
121928626  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
121923252  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121932579  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
121925257  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121925596  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121937300  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
121914625  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
121934110  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121919908  AKT3; LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121915323  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121920614  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
121934250  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
121931818  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
121916397  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
121928727  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
121919527  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
121934759  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
121930063  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
121935476  PPP1R3E; protein phosphatase 1 regulatory subunit 3E [KO:K07189]
121914974  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
121921389  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
121931852  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
121926768  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
121922692  PPP1R3F; protein phosphatase 1 regulatory subunit 3F [KO:K17453]
121916974  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
121934241  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
121937509  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
121925259  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
121936610  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
121933110  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
121930342  CALM1; calmodulin-1 [KO:K02183]
121915316  CALM3; calmodulin-3 [KO:K02183]
121921338  CALM2; calmodulin-2 [KO:K02183]
121915509  calmodulin-1 [KO:K02183]
121936891  CALML6; calmodulin-like protein 6 [KO:K02183]
121927249  glycogen phosphorylase, liver form-like [KO:K00688] [EC:2.4.1.1]
121916921  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
121915621  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
121915249  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
121928556  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
121921255  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
121914201  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
121920311  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
121921522  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
121931509  PRKAR2B; LOW QUALITY PROTEIN: cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
121915645  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
121936709  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
121925748  PRKCI; LOW QUALITY PROTEIN: protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
121934649  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191]
121916942  FLOT2; flotillin-2 isoform X1 [KO:K07192]
121922338  FLOT1; flotillin-1 isoform X1 [KO:K07192]
121917065  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
121925325  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
121916237  CBLC; E3 ubiquitin-protein ligase CBL-C isoform X1 [KO:K04707] [EC:2.3.2.27]
121934432  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
121917208  E3 ubiquitin-protein ligase CBL-B-like isoform X1 [KO:K22517] [EC:2.3.2.27]
121917254  E3 ubiquitin-protein ligase CBL-B-like isoform X1 [KO:K22517] [EC:2.3.2.27]
121932763  crk-like protein [KO:K04438]
121917039  CRK; adapter molecule crk [KO:K04438]
121917981  CRKL; crk-like protein [KO:K04438]
121936317  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
121919096  RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
121921379  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
121920227  TRIP10; cdc42-interacting protein 4 isoform X1 [KO:K07196]
121914431  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
121916866  ACACA; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
121916415  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
121922081  FASN; fatty acid synthase isoform X1 [KO:K00665] [EC:2.3.1.85]
121924101  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
121935123  HK2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
121925397  hexokinase-1 [KO:K00844] [EC:2.7.1.1]
121925398  HKDC1; hexokinase HKDC1 isoform X1 [KO:K00844] [EC:2.7.1.1]
121934329  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
121928669  PRKAA2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
121921129  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
121916459  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
121928639  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
121922773  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
121930746  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
121935662  PRKAG2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
121936517  FOXO1; forkhead box protein O1 [KO:K07201]
121930952  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
121932522  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
121933438  glucose-6-phosphatase catalytic subunit 1-like [KO:K01084] [EC:3.1.3.9]
121935131  glucose-6-phosphatase catalytic subunit 1-like [KO:K01084] [EC:3.1.3.9]
121921722  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
121923839  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
121921483  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
121929649  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
121935154  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
121936118  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
121924302  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
121917072  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
121929722  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
121923202  RPS6; 40S ribosomal protein S6 [KO:K02991]
121922423  EIF4E1B; eukaryotic translation initiation factor 4E type 1B isoform X1 [KO:K03259]
121925478  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
121931540  EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259]
121936339  TSC1; hamartin [KO:K07206]
121914529  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
121933245  RHEB; GTP-binding protein Rheb [KO:K07208]
121915058  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
121937364  SHC2; SHC-transforming protein 2 [KO:K17447]
121923451  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
121933468  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
121921457  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
121927270  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
121920742  SOS1; son of sevenless homolog 1 [KO:K03099]
121926328  HRAS; GTPase HRas [KO:K02833]
121935008  GTPase HRas [KO:K07827]
121931822  KRAS; GTPase KRas isoform X1 [KO:K07827]
121929449  NRAS; GTPase NRas [KO:K07828]
121923177  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
121930700  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
121921146  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121934449  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
121921221  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121936502  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121932739  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121916521  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121929269  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
121937070  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
121923709  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
121914826  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
121932206  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
121922796  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
121935320  suppressor of cytokine signaling 3-like [KO:K04696]
121922070  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
121928163  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
121928746  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
121923830  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121931541  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121933447  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
121925688  INPPL1; LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909] [EC:3.1.3.86]
121925149  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
sund00010  Glycolysis / Gluconeogenesis
sund00061  Fatty acid biosynthesis
sund00500  Starch and sucrose metabolism
sund04010  MAPK signaling pathway
sund04070  Phosphatidylinositol signaling system
sund04210  Apoptosis
KO pathway
ko04910   
LinkDB

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