KEGG   PATHWAY: ely04910
Entry
ely04910                    Pathway                                
Name
Insulin signaling pathway - Epinephelus lanceolatus (giant grouper)
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
ely04910  Insulin signaling pathway
ely04910

Organism
Epinephelus lanceolatus (giant grouper) [GN:ely]
Gene
117245773  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
117246042  [KO:K07191]
117246063  [KO:K07187]
117246115  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 [KO:K03259]
117246179  pygmb; phosphorylase, glycogen, muscle b [KO:K00688] [EC:2.4.1.1]
117246188  [KO:K06269] [EC:3.1.3.16]
117246218  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
117246273  badb; BCL2 associated agonist of cell death b [KO:K02158]
117246647  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
117246703  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
117246944  mapk8b; LOW QUALITY PROTEIN: mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
117247036  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
117247099  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
117247277  [KO:K04739]
117247320  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117247352  [KO:K07189]
117247387  [KO:K04438]
117247415  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
117247553  [KO:K04696]
117247560  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
117247608  g6pca.2; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
117247677  g6pca.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
117247835  [KO:K07189]
117247843  eif4e1c; eukaryotic translation initiation factor 4E family member 1c [KO:K03259]
117247924  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117248054  [KO:K01106] [EC:3.1.3.56]
117248244  [KO:K07194]
117248328  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
117248336  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117248793  pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
117248827  [KO:K06086]
117248945  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
117249252  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
117249439  ppp1r3aa; uncharacterized protein ppp1r3aa isoform X1 [KO:K07189]
117249520  socs2; suppressor of cytokine signaling 2 [KO:K04695]
117249805  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
117249939  [KO:K07187]
117250832  [KO:K02183]
117251073  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117251133  irs2b; insulin receptor substrate 2 [KO:K07187]
117251476  [KO:K17449]
117251650  [KO:K01084] [EC:3.1.3.9]
117251791  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b isoform X1 [KO:K07200]
117251861  [KO:K02183]
117251881  [KO:K03841] [EC:3.1.3.11]
117252022  [KO:K07205]
117252094  inpp5l; inositol polyphosphate-5-phosphatase A [KO:K01106] [EC:3.1.3.56]
117252119  gck; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
117252148  [KO:K06277]
117252529  [KO:K02649]
117252591  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
117252666  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
117252779  tsc1a; TSC complex subunit 1a isoform X1 [KO:K07206]
117252832  araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
117252866  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117252892  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
117253113  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
117253153  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117253221  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
117253448  [KO:K00922] [EC:2.7.1.153]
117253497  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b isoform X1 [KO:K04372] [EC:2.7.11.1]
117253800  [KO:K05695] [EC:3.1.3.48]
117253876  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
117254016  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
117254143  [KO:K02649]
117254148  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
117254181  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
117254209  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
117254318  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
117254444  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
117254893  [KO:K04694]
117254935  tsc2; tuberin isoform X1 [KO:K07207]
117255022  [KO:K00844] [EC:2.7.1.1]
117255034  [KO:K00844] [EC:2.7.1.1]
117255058  [KO:K03099]
117255147  rptor; regulatory-associated protein of mTOR [KO:K07204]
117255306  [KO:K00844] [EC:2.7.1.1]
117255397  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117255522  trip10b; thyroid hormone receptor interactor 10b isoform X1 [KO:K07196]
117255533  [KO:K04688] [EC:2.7.11.1]
117255629  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117255631  rps6; 40S ribosomal protein S6 [KO:K02991]
117256422  ppp1r3db; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
117256979  [KO:K02183]
117257295  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
117257414  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
117257490  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
117257496  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
117257511  prkar2ab; protein kinase, cAMP-dependent, regulatory, type II, alpha, B [KO:K04739]
117257653  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
117257756  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
117258232  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
117258233  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
117258263  [KO:K05696] [EC:3.1.3.48]
117258353  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
117258381  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
117258505  [KO:K07189]
117258562  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
117258881  [KO:K07203] [EC:2.7.11.1]
117258945  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
117259021  socs4; suppressor of cytokine signaling 4 [KO:K04697]
117259426  [KO:K07189]
117259591  [KO:K04688] [EC:2.7.11.1]
117259724  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
117259781  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
117259836  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
117259841  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117259860  [KO:K07193]
117259865  foxo1a; forkhead box protein O1-A [KO:K07201]
117259974  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
117259975  [KO:K07192]
117260119  phkg1a; phosphorylase kinase, gamma 1a (muscle) [KO:K00871] [EC:2.7.11.19]
117260317  crk; adapter molecule crk [KO:K04438]
117260760  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
117260815  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
117260935  inppl1b; inositol polyphosphate phosphatase-like 1b [KO:K15909] [EC:3.1.3.86]
117261006  [KO:K03259]
117261385  insb; preproinsulin b [KO:K04526]
117261975  calml4b; calmodulin-like protein 4 [KO:K02183]
117262168  kras; GTPase KRas isoform X1 [KO:K07827]
117262356  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117262369  [KO:K02833]
117262753  [KO:K04739]
117263376  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
117263640  [KO:K07200]
117263762  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
117263881  flot1a; flotillin-1a isoform X1 [KO:K07192]
117264442  [KO:K07201]
117264673  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
117265042  [KO:K07200]
117265729  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
117265772  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
117266336  flot1b; flotillin-1b [KO:K07192]
117266754  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
117267056  calm1a; calmodulin-1a [KO:K02183]
117267058  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117267154  sos2; son of sevenless homolog 2 [KO:K03099]
117267332  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
117267401  [KO:K06269] [EC:3.1.3.16]
117267747  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
117267878  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
117268077  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
117268089  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
117268130  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
117268156  [KO:K04456] [EC:2.7.11.1]
117268290  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117268368  [KO:K04739]
117268371  zgc:55558; GTPase HRas [KO:K07827]
117268372  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
117268541  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
117268590  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
117268659  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
117268774  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
117268811  [KO:K01084] [EC:3.1.3.9]
117268906  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
117269000  [KO:K04707] [EC:2.3.2.27]
117269207  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
117269441  [KO:K07205]
117269552  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117269588  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X1 [KO:K06277]
117269589  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
117269635  tsc1b; TSC complex subunit 1b isoform X1 [KO:K07206]
117269677  crkl; crk-like protein [KO:K04438]
117269772  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
117269870  [KO:K07192]
117269992  shc3; SHC-transforming protein 3 [KO:K17448]
117270152  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
117270220  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
117270452  ins; insulin [KO:K04526]
117270599  [KO:K02183]
117270623  cblb; E3 ubiquitin-protein ligase CBL-B-B [KO:K22517] [EC:2.3.2.27]
117270724  [KO:K06269] [EC:3.1.3.16]
117271479  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b isoform X1 [KO:K04369] [EC:2.7.12.2]
117271502  [KO:K02649]
117271508  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
117271532  insra; insulin receptor a [KO:K04527] [EC:2.7.10.1]
117271818  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
117271943  [KO:K00922] [EC:2.7.1.153]
117272041  [KO:K05695] [EC:3.1.3.48]
117272131  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
117272283  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
117272303  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
117272364  rheb; GTP-binding protein Rheb [KO:K07208]
117272382  [KO:K00844] [EC:2.7.1.1]
117272897  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
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
ely00010  Glycolysis / Gluconeogenesis
ely00061  Fatty acid biosynthesis
ely00500  Starch and sucrose metabolism
ely04010  MAPK signaling pathway
ely04070  Phosphatidylinositol signaling system
ely04210  Apoptosis
KO pathway
ko04910   

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