KEGG   PATHWAY: bpec04910
Entry
bpec04910                   Pathway                                
Name
Insulin signaling pathway - Boleophthalmus pectinirostris (great blue-spotted mudskipper)
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
bpec04910  Insulin signaling pathway
bpec04910

Organism
Boleophthalmus pectinirostris (great blue-spotted mudskipper) [GN:bpec]
Gene
110156469  insulin-like [KO:K04526]
110172772  insulin-1-like [KO:K04526]
110164155  insulin receptor-like [KO:K04527] [EC:2.7.10.1]
110160177  insulin receptor-like [KO:K04527] [EC:2.7.10.1]
110158597  insulin receptor substrate 1-B-like [KO:K16172]
110157680  insulin receptor substrate 1-B-like [KO:K16172]
110153857  insulin receptor substrate 2-B-like [KO:K07187]
110165987  insulin receptor substrate 2-like [KO:K07187]
110173115  irs2; insulin receptor substrate 2 [KO:K07187]
110174798  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
110170692  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
110157584  phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
110167868  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
110173441  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
110165671  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
110160467  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
110164593  pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
110153584  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110173447  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110174559  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
110159640  pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
110162042  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110169010  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
110155946  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
110155274  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110156798  akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110166530  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
110172488  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
110158208  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
110163334  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
110168800  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
110171048  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
110153634  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
110167732  serine/threonine-protein phosphatase PP1-alpha catalytic subunit-like isoform X1 [KO:K06269] [EC:3.1.3.16]
110164831  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
110175397  protein phosphatase 1 regulatory subunit 3E-like [KO:K07189]
110166355  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
110154510  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
110154511  ppp1r3c; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
110161905  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
110165740  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
110159624  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
110154096  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform-like [KO:K00871] [EC:2.7.11.19]
110153817  phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
110172836  LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, liver isoform-like [KO:K07190]
110175269  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
110162823  calm1; calmodulin [KO:K02183]
110168743  calml6; calmodulin-like protein 6 [KO:K02183]
110173356  calmodulin-like protein 4 [KO:K02183]
110159371  calmodulin-like protein 4 [KO:K02183]
110155219  calmodulin-alpha-like [KO:K02183]
110170100  calmodulin-alpha-like [KO:K02183]
110154102  calm3; calmodulin isoform X1 [KO:K02183]
110170717  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
110158625  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
110167128  glycogen phosphorylase, liver form-like [KO:K00688] [EC:2.4.1.1]
110172817  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
110166277  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
110166288  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
110160084  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110157202  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
110169686  LOW QUALITY PROTEIN: cAMP-dependent protein kinase type II-beta regulatory subunit-like [KO:K04739]
110167294  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
110168510  cAMP-dependent protein kinase type II-alpha regulatory subunit-like [KO:K04739]
110168777  prkar2a; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
110159608  prkar1a; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
110168856  hormone-sensitive lipase-like isoform X1 [KO:K07188] [EC:3.1.1.79]
110174235  lipe; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
110175813  protein kinase C zeta type-like [KO:K18952] [EC:2.7.11.13]
110164081  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
110159470  slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
110165105  flot2; flotillin-2 [KO:K07192]
110168897  flotillin-1 [KO:K07192]
110162990  flotillin-1-like [KO:K07192]
110163693  sh2b2; SH2B adapter protein 2 [KO:K07193]
110162295  sorbin and SH3 domain-containing protein 1-like [KO:K06086]
110174966  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
110154105  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
110169053  cblb; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
110160359  crk; adapter molecule crk [KO:K04438]
110166352  crkl; crk-like protein [KO:K04438]
110157298  rapgef1; rap guanine nucleotide exchange factor 1 [KO:K06277]
110170252  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
110165449  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
110153510  cdc42-interacting protein 4 homolog [KO:K07196]
110166559  trip10; cdc42-interacting protein 4 isoform X1 [KO:K07196]
110171451  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
110168168  acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
110156685  acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
110154166  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
110175417  hexokinase-1-like isoform X1 [KO:K00844] [EC:2.7.1.1]
110175418  putative hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
110156472  hexokinase-2-like [KO:K00844] [EC:2.7.1.1]
110163429  hexokinase-2-like [KO:K00844] [EC:2.7.1.1]
110155995  hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
110153979  gck; glucokinase [KO:K12407] [EC:2.7.1.2]
110157325  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
110154939  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
110158108  5'-AMP-activated protein kinase subunit beta-2-like [KO:K07199]
110163374  5'-AMP-activated protein kinase subunit beta-1-like isoform X1 [KO:K07199]
110166356  5'-AMP-activated protein kinase subunit beta-1-like [KO:K07199]
110156174  5'-AMP-activated protein kinase subunit gamma-3-like [KO:K07200]
110167659  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
110168389  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
110157254  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
110168978  5'-AMP-activated protein kinase subunit gamma-3-like [KO:K07200]
110164373  foxo1; forkhead box protein O1 [KO:K07201]
110158469  forkhead box protein O1-A-like [KO:K07201]
110159306  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
110154170  glucose-6-phosphatase-like [KO:K01084] [EC:3.1.3.9]
110154257  glucose-6-phosphatase-like isoform X1 [KO:K01084] [EC:3.1.3.9]
110154313  glucose-6-phosphatase 3-like [KO:K01084] [EC:3.1.3.9]
110157379  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
110163635  fructose-1,6-bisphosphatase isozyme 2-like [KO:K03841] [EC:3.1.3.11]
110163482  fructose-1,6-bisphosphatase 1-like isoform X1 [KO:K03841] [EC:3.1.3.11]
110162522  phosphoenolpyruvate carboxykinase, cytosolic [GTP]-like [KO:K01596] [EC:4.1.1.32]
110166310  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
110157966  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110173825  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
110171872  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
110165065  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
110159891  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
110165312  rps6; 40S ribosomal protein S6 [KO:K02991]
110166384  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
110172485  eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
110155371  eukaryotic translation initiation factor 4E-1A-like [KO:K03259]
110153721  eukaryotic translation initiation factor 4E-1A-like [KO:K03259]
110164231  eukaryotic translation initiation factor 4E-like [KO:K03259]
110168809  hamartin-like isoform X1 [KO:K07206]
110161175  tsc1; hamartin [KO:K07206]
110166137  tuberin-like [KO:K07207]
110165184  tuberin-like [KO:K07207]
110153468  rheb; GTP-binding protein Rheb [KO:K07208]
110168392  GTP-binding protein Rheb-like [KO:K07208]
110172731  bcl2-associated agonist of cell death-like [KO:K02158]
110156254  bcl2-associated agonist of cell death-like [KO:K02158]
110162980  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
110173049  shc4; SHC-transforming protein 4 [KO:K06279]
110167820  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
110160455  SHC-transforming protein 3-like [KO:K17448]
110155075  grb2; growth factor receptor-bound protein 2 [KO:K04364]
110163236  sos2; son of sevenless homolog 2 [KO:K03099]
110169298  hras; GTPase HRas [KO:K02833]
110170289  kras; GTPase KRas isoform X1 [KO:K07827]
110158202  GTPase HRas-like [KO:K07827]
110162179  serine/threonine-protein kinase A-Raf-like [KO:K08845] [EC:2.7.11.1]
110162539  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
110164922  raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
110160811  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110173999  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
110158255  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
110155433  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110167739  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
110167946  mknk2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
110158113  ETS domain-containing protein Elk-3-like [KO:K04375]
110155763  socs1; suppressor of cytokine signaling 1 [KO:K04694]
110153535  suppressor of cytokine signaling 1-like [KO:K04694]
110161754  suppressor of cytokine signaling 2-like [KO:K04695]
110168324  suppressor of cytokine signaling 3-like [KO:K04696]
110167423  suppressor of cytokine signaling 3-like [KO:K04696]
110164566  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
110174624  receptor-type tyrosine-protein phosphatase S-like [KO:K05695] [EC:3.1.3.48]
110164091  ptprf; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
110159805  mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
110157114  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
110160610  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
110157667  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
110155462  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
110174275  inppl1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909] [EC:3.1.3.86]
110158855  phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2B-like [KO:K15909] [EC:3.1.3.86]
110166333  inpp5a; type I inositol 1,4,5-trisphosphate 5-phosphatase [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
bpec00010  Glycolysis / Gluconeogenesis
bpec00061  Fatty acid biosynthesis
bpec00500  Starch and sucrose metabolism
bpec04010  MAPK signaling pathway
bpec04070  Phosphatidylinositol signaling system
bpec04210  Apoptosis
KO pathway
ko04910   
LinkDB

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