KEGG   PATHWAY: fca04910
Entry
fca04910                    Pathway                                
Name
Insulin signaling pathway - Felis catus (domestic cat)
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
fca04910  Insulin signaling pathway
fca04910

Organism
Felis catus (domestic cat) [GN:fca]
Gene
100037406  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
100127108  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
100270775  FASN; fatty acid synthase isoform X1 [KO:K00665] [EC:2.3.1.85]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101080351  [KO:K02991]
101080358  HK3; hexokinase-3 [KO:K00844] [EC:2.7.1.1]
101080377  EIF4E; eukaryotic translation initiation factor 4E isoform X2 [KO:K03259]
101080974  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
101080980  SOCS2; suppressor of cytokine signaling 2 isoform X2 [KO:K04695]
101081127  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit isoform X2 [KO:K04739]
101081184  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
101081238  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
101081387  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X3 [KO:K04368] [EC:2.7.12.2]
101081534  CALM2; calmodulin-2 [KO:K02183]
101081660  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101081802  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X3 [KO:K07202]
101081846  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101082505  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X5 [KO:K04372] [EC:2.7.11.1]
101082969  TSC2; tuberin isoform X1 [KO:K07207]
101083037  INPP5A; inositol polyphosphate-5-phosphatase A isoform X2 [KO:K01106] [EC:3.1.3.56]
101083046  ACACA; acetyl-CoA carboxylase 1 isoform X7 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101083160  RHEB; GTP-binding protein Rheb [KO:K07208]
101083489  SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447]
101083815  EXOC7; exocyst complex component 7 isoform X5 [KO:K07195]
101084485  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
101084578  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101084601  PPP1R3F; protein phosphatase 1 regulatory subunit 3F [KO:K17453]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101084832  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101084864  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
101084908  CRKL; crk-like protein isoform X1 [KO:K04438]
101085259  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X2 [KO:K04739]
101085486  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
101086100  CRK; adapter molecule crk isoform X1 [KO:K04438]
101086645  RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
101086680  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101086715  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
101086824  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
101086862  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
101087000  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
101087206  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K04372] [EC:2.7.11.1]
101087257  IRS1; insulin receptor substrate 1 [KO:K16172]
101087535  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087851  PRKCZ; protein kinase C zeta type isoform X3 [KO:K18952] [EC:2.7.11.13]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101088140  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
101088459  PKLR; pyruvate kinase PKLR isoform X2 [KO:K12406] [EC:2.7.1.40]
101088570  PPP1R3B; protein phosphatase 1 regulatory subunit 3B isoform X2 [KO:K07189]
101088571  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101088632  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
101088635  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
101088727  TRIP10; cdc42-interacting protein 4 isoform X1 [KO:K07196]
101088847  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101089256  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
101089344  HK2; hexokinase-2 isoform X3 [KO:K00844] [EC:2.7.1.1]
101089364  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
101089839  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
101090050  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X16 [KO:K06086]
101090410  SH2B2; SH2B adapter protein 2 isoform X3 [KO:K07193]
101090494  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
101091063  CALM3; calmodulin-3 [KO:K02183]
101091099  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101091812  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X3 [KO:K04688] [EC:2.7.11.1]
101091892  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101092123  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
101092204  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X3 [KO:K07200]
101092284  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X3 [KO:K07199]
101092346  BRAF; serine/threonine-protein kinase B-raf isoform X5 [KO:K04365] [EC:2.7.11.1]
101092561  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X2 [KO:K04688] [EC:2.7.11.1]
101092572  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101092911  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
101092932  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101093251  IRS4; insulin receptor substrate 4 [KO:K17446]
101093286  [KO:K02649]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101094051  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101094274  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101094295  HKDC1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
101094679  CALM1; calmodulin-1 [KO:K02183]
101094684  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
101094877  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
101095139  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
101095156  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
101095208  FLOT2; flotillin-2 isoform X1 [KO:K07192]
101095353  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101095500  PPP1R3E; protein phosphatase 1 regulatory subunit 3E [KO:K07189]
101095611  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
101095791  IRS2; insulin receptor substrate 2 [KO:K07187]
101095865  SHC3; SHC-transforming protein 3 [KO:K17448]
101095885  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X3 [KO:K07198] [EC:2.7.11.31]
101096000  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
101096047  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101096063  FLOT1; flotillin-1 isoform X1 [KO:K07192]
101096508  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
101096628  FOXO1; forkhead box protein O1 [KO:K07201]
101096789  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101097703  [KO:K02183]
101097770  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
101098152  MTOR; serine/threonine-protein kinase mTOR isoform X3 [KO:K07203] [EC:2.7.11.1]
101098403  HK1; hexokinase-1 isoform X2 [KO:K00844] [EC:2.7.1.1]
101098495  RPS6; 40S ribosomal protein S6 [KO:K02991]
101098862  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101098874  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
101099050  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
101099142  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
101099307  [KO:K02183]
101099507  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
101099626  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
101099916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
101100119  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
101100185  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
101100190  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
101100214  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101100281  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101100432  [KO:K17445]
101100682  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
101100836  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
101100922  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
101101498  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
101101514  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
101101686  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X3 [KO:K06276] [EC:2.7.11.1]
102902667  [KO:K02183]
109492306  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
111558242  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
493804  INS; insulin precursor [KO:K04526]
723970  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
751103  HRAS; GTPase HRas isoform X1 [KO:K02833]
751104  KRAS; GTPase KRas isoform X2 [KO:K07827]
751105  NRAS; GTPase NRas [KO:K07828]
751818  LIPE; hormone-sensitive lipase isoform X3 [KO:K07188] [EC:3.1.1.79]
768269  BAD; bcl2-associated agonist of cell death [KO:K02158]
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
fca00010  Glycolysis / Gluconeogenesis
fca00061  Fatty acid biosynthesis
fca00500  Starch and sucrose metabolism
fca04010  MAPK signaling pathway
fca04070  Phosphatidylinositol signaling system
fca04210  Apoptosis
KO pathway
ko04910   

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