KEGG   PATHWAY: efo04910
Entry
efo04910                    Pathway                                
Name
Insulin signaling pathway - Epinephelus fuscoguttatus (brown-marbled 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
efo04910  Insulin signaling pathway
efo04910

Organism
Epinephelus fuscoguttatus (brown-marbled grouper) [GN:efo]
Gene
125898795  ins; insulin [KO:K04526]
125894470  insb; preproinsulin b [KO:K04526]
125901820  insra; insulin receptor a [KO:K04527] [EC:2.7.10.1]
125895265  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
125883633  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
125898921  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
125884378  insulin receptor substrate 2-B [KO:K07187]
125884695  insulin receptor substrate 2-like isoform X1 [KO:K07187]
125899435  irs2b; insulin receptor substrate 2 [KO:K07187]
125902071  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
125896428  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
125890643  phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
125905500  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125895325  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
125901675  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125895453  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
125901864  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125885349  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
125891486  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125888244  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125880414  pdpk1b; 3-phosphoinositide dependent protein kinase 1b [KO:K06276] [EC:2.7.11.1]
125903284  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125885562  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125898179  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
125900668  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125888855  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125900028  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125882641  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
125880004  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
125883517  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
125890352  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
125897624  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
125879522  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
125880495  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
125901054  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
125882096  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
125882629  ppp1r3aa; uncharacterized protein ppp1r3aa isoform X1 [KO:K07189]
125890376  ppp1r3c2b; protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
125891384  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
125903674  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
125891806  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
125886879  ppp1r3db; protein phosphatase 1, regulatory subunit 3Db [KO:K07189]
125906245  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
125880580  protein phosphatase 1 regulatory subunit 3C-B-like isoform X1 [KO:K07189]
125880974  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
125888614  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform-like [KO:K00871] [EC:2.7.11.19]
125884380  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
125904419  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
125898838  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
125882506  calml4a; calmodulin-like protein 4a [KO:K02183]
125897124  calmodulin-1 [KO:K02183]
125903442  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
125887226  calglandulin-like isoform X1 [KO:K02183]
125888087  calml4b; calmodulin-like protein 4 [KO:K02183]
125900581  calm1a; calmodulin-1a [KO:K02183]
125888709  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
125883891  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
125903008  pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
125898907  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
125900736  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
125901417  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
125895468  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
125902200  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
125885389  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
125879778  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
125891128  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
125878846  cAMP-dependent protein kinase type I-alpha regulatory subunit-like isoform X1 [KO:K04739]
125892795  cAMP-dependent protein kinase type II-alpha regulatory subunit-like isoform X1 [KO:K04739]
125879689  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
125880548  cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
125904660  lipea; lipase, hormone-sensitive a isoform X1 [KO:K07188] [EC:3.1.1.79]
125892771  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
125891995  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
125902012  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
125883674  solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
125904837  flot1a; flotillin-1a [KO:K07192]
125898570  flotillin-2a-like [KO:K07192]
125893140  flot1b; flotillin-1b [KO:K07192]
125888759  flotillin-2 [KO:K07192]
125888802  SH2B adapter protein 2 [KO:K07193]
125904066  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
125898957  E3 ubiquitin-protein ligase CBL-like isoform X1 [KO:K04707] [EC:2.3.2.27]
125888610  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
125898591  cblb; E3 ubiquitin-protein ligase CBL-B-B [KO:K22517] [EC:2.3.2.27]
125889182  crk; adapter molecule crk [KO:K04438]
125898975  adapter molecule crk-like [KO:K04438]
125906119  crkl; crk-like protein [KO:K04438]
125890857  rap guanine nucleotide exchange factor 1-like isoform X1 [KO:K06277]
125906344  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X1 [KO:K06277]
125903145  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
125880637  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
125878926  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
125886206  trip10b; thyroid hormone receptor interactor 10b [KO:K07196]
125880123  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
125897833  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125889833  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125880982  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
125882877  hexokinase-1-like [KO:K00844] [EC:2.7.1.1]
125889805  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
125897900  hexokinase-4-like [KO:K00844] [EC:2.7.1.1]
125881853  hexokinase HKDC1-like [KO:K00844] [EC:2.7.1.1]
125881861  hexokinase-1 [KO:K00844] [EC:2.7.1.1]
125890055  gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
125895929  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
125905972  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
125901835  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
125889962  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
125905525  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
125901833  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
125884947  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
125900205  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b isoform X1 [KO:K07200]
125888481  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
125898818  forkhead box protein O1-A-like [KO:K07201]
125888651  foxo1a; forkhead box protein O1-A [KO:K07201]
125883543  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
125878857  glucose-6-phosphatase catalytic subunit 1-like [KO:K01084] [EC:3.1.3.9]
125899216  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
125880315  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
125881339  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
125881340  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
125890130  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
125890131  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
125905974  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
125882212  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
125896920  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
125891637  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
125885745  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
125897914  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
125886237  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
125888620  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
125886008  rps6; 40S ribosomal protein S6 [KO:K02991]
125890656  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
125878595  eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
125902855  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
125903737  eif4e1c; eukaryotic translation initiation factor 4E family member 1c [KO:K03259]
125885371  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 [KO:K03259]
125894045  eukaryotic translation initiation factor 4E-1A-like [KO:K03259]
125900409  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
125890855  tsc1a; TSC complex subunit 1a isoform X1 [KO:K07206]
125905504  tsc1b; TSC complex subunit 1b [KO:K07206]
125886310  tsc2; tuberin isoform X1 [KO:K07207]
125902502  rheb; GTP-binding protein Rheb [KO:K07208]
125888406  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
125883566  badb; BCL2 associated agonist of cell death b [KO:K02158]
125892594  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
125895735  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
125905484  shc3; SHC-transforming protein 3 [KO:K17448]
125902985  SHC-transforming protein 1-like isoform X1 [KO:K17449]
125885663  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
125879149  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
125885879  son of sevenless homolog 1-like isoform X1 [KO:K03099]
125900475  sos2; son of sevenless homolog 2 [KO:K03099]
125887517  GTPase HRas [KO:K02833]
125880010  zgc:55558; GTPase KRas [KO:K07827]
125887085  kras; GTPase KRas isoform X1 [KO:K07827]
125890244  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
125882719  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
125891335  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
125888135  map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125895747  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
125902384  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b isoform X1 [KO:K04369] [EC:2.7.12.2]
125890125  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125878991  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125896016  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
125896466  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
125891334  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
125885736  suppressor of cytokine signaling 1-like [KO:K04694]
125880011  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
125883111  socs2; suppressor of cytokine signaling 2 [KO:K04695]
125879715  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
125881157  suppressor of cytokine signaling 3-like [KO:K04696]
125903782  socs4; suppressor of cytokine signaling 4 [KO:K04697]
125891908  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
125902848  receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
125903016  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125905962  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125880486  mapk8b; LOW QUALITY PROTEIN: mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
125894559  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
125889921  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
125888890  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
125894975  inppl1b; inositol polyphosphate phosphatase-like 1b [KO:K15909] [EC:3.1.3.86]
125903575  inositol polyphosphate-5-phosphatase A isoform X1 [KO:K01106] [EC:3.1.3.56]
125890373  inpp5l; inositol polyphosphate-5-phosphatase A [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
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Ogawa W, Kasuga M.
  Title
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Reference
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Reference
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Reference
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Reference
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Reference
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Reference
PMID:9445476
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Phosphorylation and activation of p70s6k by PDK1.
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Science 279:707-10 (1998)
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Reference
PMID:9609110
  Authors
Ogawa W, Matozaki T, Kasuga M.
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Role of binding proteins to IRS-1 in insulin signalling.
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Mol Cell Biochem 182:13-22 (1998)
Reference
PMID:9609111
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Insulin regulation of the Ras activation/inactivation cycle.
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Mol Cell Biochem 182:23-9 (1998)
Reference
PMID:15229476
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Insulin-like growth factors and neoplasia.
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Nat Rev Cancer 4:505-18 (2004)
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Reference
PMID:9346240
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Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.
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Cell 91:231-41 (1997)
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Reference
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Horm Res 68:72-82 (2007)
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Reference
PMID:18291668
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  Title
SREBPs: the crossroads of physiological and pathological lipid homeostasis.
  Journal
Trends Endocrinol Metab 19:65-73 (2008)
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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
efo00010  Glycolysis / Gluconeogenesis
efo00061  Fatty acid biosynthesis
efo00500  Starch and sucrose metabolism
efo04010  MAPK signaling pathway
efo04070  Phosphatidylinositol signaling system
efo04210  Apoptosis
KO pathway
ko04910   
LinkDB

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