KEGG   PATHWAY: nvs04910
Entry
nvs04910                    Pathway                                
Name
Insulin signaling pathway - Neogale vison (American mink)
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
nvs04910  Insulin signaling pathway
nvs04910

Organism
Neogale vison (American mink) [GN:nvs]
Gene
122889362  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
122889452  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122889856  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
122889886  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
122889951  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
122890143  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
122891238  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
122891254  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
122891437  SOCS2; suppressor of cytokine signaling 2 isoform X1 [KO:K04695]
122891509  [KO:K02183]
122891793  CALML3; calmodulin-like protein 3 [KO:K02183]
122892422  HK3; hexokinase-3 [KO:K00844] [EC:2.7.1.1]
122892446  KRAS; GTPase KRas isoform X1 [KO:K07827]
122892965  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
122893081  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
122893234  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
122893678  PPP1R3E; protein phosphatase 1 regulatory subunit 3E [KO:K07189]
122893865  CALML4; calmodulin-like protein 4 [KO:K02183]
122894114  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
122894172  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122894205  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
122894274  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
122894399  CALM1; calmodulin-1 [KO:K02183]
122894750  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
122895321  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
122895342  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122895378  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
122895511  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
122895733  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
122895932  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
122896052  [KO:K17445]
122896129  TSC2; tuberin isoform X1 [KO:K07207]
122896190  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
122896725  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
122897033  PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453]
122897407  IRS4; insulin receptor substrate 4 [KO:K17446]
122897535  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
122897579  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
122897658  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
122897992  [KO:K03259]
122898670  CALML6; calmodulin-like protein 6 [KO:K02183]
122899136  [KO:K07828]
122899350  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
122899425  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122899446  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122899864  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
122899916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122899928  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
122900018  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
122900129  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
122900359  NRAS; GTPase NRas [KO:K07828]
122900404  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
122900744  HKDC1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
122900745  HK1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
122900866  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122900922  PPP1R3C; protein phosphatase 1 regulatory subunit 3C isoform X1 [KO:K07189]
122900951  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
122901232  INPP5A; inositol polyphosphate-5-phosphatase A isoform X1 [KO:K01106] [EC:3.1.3.56]
122901740  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
122901791  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
122901830  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
122902369  IRS1; insulin receptor substrate 1 [KO:K16172]
122902422  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
122903191  CRKL; crk-like protein [KO:K04438]
122903200  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122903326  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
122903371  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
122903431  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
122904101  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
122904707  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
122905138  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122905216  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
122905217  RHEB; GTP-binding protein Rheb [KO:K07208]
122905382  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
122905866  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
122905906  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
122905934  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
122905963  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
122905991  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
122906050  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit isoform X1 [KO:K04739]
122906150  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
122906169  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
122906356  CRK; adapter molecule crk isoform X1 [KO:K04438]
122906396  FLOT2; flotillin-2 isoform X1 [KO:K07192]
122906479  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
122906505  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122906692  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
122906856  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
122907042  FOXO1; forkhead box protein O1 [KO:K07201]
122907240  IRS2; insulin receptor substrate 2 [KO:K07187]
122907697  [KO:K03259]
122908475  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
122908538  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
122908688  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
122908712  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122908899  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122909192  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122909447  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
122909588  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122909651  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
122909778  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
122909814  TRIP10; cdc42-interacting protein 4 isoform X1 [KO:K07196]
122909871  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122909991  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
122911475  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
122911840  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
122911918  CALM3; calmodulin-3 [KO:K02183]
122912036  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122912061  FLOT1; flotillin-1 isoform X1 [KO:K07192]
122912071  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
122912363  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
122912620  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
122912745  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
122913061  BAD; bcl2-associated agonist of cell death [KO:K02158]
122913072  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
122913185  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
122913186  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
122913220  HRAS; GTPase HRas isoform X1 [KO:K02833]
122914590  INS; insulin [KO:K04526]
122915030  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
122915138  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
122915195  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
122915651  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122915922  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
122915943  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
122915978  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
122916364  RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
122916371  CALM2; calmodulin-2 [KO:K02183]
122916432  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
122916957  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
122917138  TSC1; hamartin [KO:K07206]
122917147  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
122917575  RPS6; 40S ribosomal protein S6 [KO:K02991]
122917635  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
122917799  SHC3; SHC-transforming protein 3 [KO:K17448]
122918258  PKLR; pyruvate kinase PKLR isoform X1 [KO:K12406] [EC:2.7.1.40]
122918524  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122918946  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
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
nvs00010  Glycolysis / Gluconeogenesis
nvs00061  Fatty acid biosynthesis
nvs00500  Starch and sucrose metabolism
nvs04010  MAPK signaling pathway
nvs04070  Phosphatidylinositol signaling system
nvs04210  Apoptosis
KO pathway
ko04910   

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