KEGG   PATHWAY: ajm04910
Entry
ajm04910                    Pathway                                
Name
Insulin signaling pathway - Artibeus jamaicensis (Jamaican fruit-eating bat)
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
ajm04910  Insulin signaling pathway
ajm04910

Organism
Artibeus jamaicensis (Jamaican fruit-eating bat) [GN:ajm]
Gene
119036351  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
119036586  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
119036810  PPP1R3B; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
119037164  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
119037276  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X2 [KO:K01596] [EC:4.1.1.32]
119037489  FOXO1; forkhead box protein O1 [KO:K07201]
119037894  CALM1; calmodulin-1 [KO:K02183]
119038115  HK1; hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
119038131  HKDC1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
119038386  HK2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
119038781  [KO:K02991]
119038902  CRKL; crk-like protein [KO:K04438]
119039259  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
119039260  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
119039580  RPS6; 40S ribosomal protein S6 isoform X1 [KO:K02991]
119039718  PKLR; pyruvate kinase PKLR isoform X1 [KO:K12406] [EC:2.7.1.40]
119039770  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
119040345  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
119040363  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
119040451  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
119040479  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119040627  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
119040664  CRK; adapter molecule crk isoform X1 [KO:K04438]
119040893  PPP1R3A; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
119040930  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119040940  SHC3; SHC-transforming protein 3 [KO:K17448]
119041006  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
119041148  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
119041711  NRAS; GTPase NRas [KO:K07828]
119041793  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
119041842  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
119041883  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
119042112  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
119042297  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
119042545  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
119042614  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
119042698  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
119042788  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
119043036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119043456  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
119043765  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
119043820  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K04372] [EC:2.7.11.1]
119044252  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X2 [KO:K07198] [EC:2.7.11.31]
119044502  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
119044503  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
119044619  SHC2; SHC-transforming protein 2 [KO:K17447]
119044712  SH2B2; SH2B adapter protein 2 isoform X2 [KO:K07193]
119044737  IRS1; insulin receptor substrate 1 [KO:K16172]
119044815  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
119044861  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119045082  [KO:K04372] [EC:2.7.11.1]
119045329  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
119045448  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
119045845  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
119046025  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
119046347  FLOT1; flotillin-1 isoform X1 [KO:K07192]
119046526  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
119046830  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119046845  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119047140  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
119047956  PPP1R3E; protein phosphatase 1 regulatory subunit 3E [KO:K07189]
119048987  KRAS; GTPase KRas isoform X1 [KO:K07827]
119048988  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
119049465  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
119049690  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119050292  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
119050357  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
119050509  CALML6; calmodulin-like protein 6 [KO:K02183]
119050546  PRKCZ; protein kinase C zeta type isoform X2 [KO:K18952] [EC:2.7.11.13]
119050746  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
119051651  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
119051804  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
119052051  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
119052184  PTPRF; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
119052227  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119053036  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
119053073  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
119053288  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119053408  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119053594  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
119054312  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X4 [KO:K03259]
119055031  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
119055335  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
119055814  [KO:K04695]
119056023  TRIP10; cdc42-interacting protein 4 isoform X1 [KO:K07196]
119056633  CALM3; calmodulin-3 [KO:K02183]
119056888  PRKAG3; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
119056966  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
119057045  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
119057055  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
119057101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119057111  CALML4; calmodulin-like protein 4 isoform X4 [KO:K02183]
119057312  [KO:K02183]
119057414  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119057456  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
119057541  INS; insulin [KO:K04526]
119057612  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
119057735  [KO:K02183]
119057758  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
119058052  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
119058207  TSC2; tuberin isoform X3 [KO:K07207]
119058372  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
119058513  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
119058521  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
119058525  EXOC7; exocyst complex component 7 isoform X2 [KO:K07195]
119058629  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
119058654  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
119059006  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X5 [KO:K06277]
119059019  TSC1; hamartin isoform X1 [KO:K07206]
119059157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119059198  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119059472  PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453]
119059475  INPP5A; inositol polyphosphate-5-phosphatase A isoform X1 [KO:K01106] [EC:3.1.3.56]
119060124  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
119060132  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
119060144  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
119060868  RHOQ; rho-related GTP-binding protein RhoQ [KO:K07194]
119060885  CALM2; calmodulin-2 [KO:K02183]
119061761  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
119062033  FLOT2; flotillin-2 isoform X1 [KO:K07192]
119062206  HRAS; GTPase HRas isoform X1 [KO:K02833]
119062281  SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
119062679  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119062708  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119062834  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
119062886  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
119062958  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
119062960  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
119063115  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119063754  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119064071  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
119064089  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119064562  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
119065028  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
119065177  IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
119065325  PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X1 [KO:K05696] [EC:3.1.3.48]
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
ajm00010  Glycolysis / Gluconeogenesis
ajm00061  Fatty acid biosynthesis
ajm00500  Starch and sucrose metabolism
ajm04010  MAPK signaling pathway
ajm04070  Phosphatidylinositol signaling system
ajm04210  Apoptosis
KO pathway
ko04910   

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