KEGG   PATHWAY: psex04910
Entry
psex04910                   Pathway                                
Name
Insulin signaling pathway - Polypterus senegalus (gray bichir)
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
psex04910  Insulin signaling pathway
psex04910

Organism
Polypterus senegalus (gray bichir) [GN:psex]
Gene
120542969  insulin [KO:K04526]
120517688  ins; insulin [KO:K04526]
120537652  insulin receptor-like [KO:K04527] [EC:2.7.10.1]
120533058  irs1; insulin receptor substrate 1-B [KO:K16172]
120524638  irs2b; insulin receptor substrate 2 [KO:K07187]
120537570  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120514216  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
120532558  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120530839  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
120530887  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
120525111  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
120532592  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120542912  3-phosphoinositide-dependent protein kinase 1-like [KO:K06276] [EC:2.7.11.1]
120538705  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120516788  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120522916  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120539544  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
120543187  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
120538109  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
120539258  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
120540964  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
120526412  ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
120536411  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
120538942  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
120514703  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
120540859  ppp1r3cb; protein phosphatase 1 regulatory subunit 3C-B [KO:K07189]
120527208  ppp1r3b; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
120535489  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
120531507  phkg1b; phosphorylase kinase, gamma 1b (muscle) [KO:K00871] [EC:2.7.11.19]
120536637  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
120523590  phosphorylase b kinase regulatory subunit alpha, liver isoform-like isoform X1 [KO:K07190]
120535345  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
120529801  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
120530526  calglandulin-like [KO:K02183]
120521606  calmodulin-like [KO:K02183]
120538670  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
120539370  calm3b; calmodulin 3b (phosphorylase kinase, delta) [KO:K02183]
120523494  calmodulin-alpha-like [KO:K02183]
120541657  calml4a; calmodulin-like protein 4a [KO:K02183]
120516414  calmodulin-alpha-like [KO:K02183]
120516454  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
120516564  calmodulin-like [KO:K02183]
120516565  calmodulin-like [KO:K02183]
120518519  calmodulin-1 [KO:K02183]
120539269  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
120517027  pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
120518381  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
120516860  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
120514851  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
120541109  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
120534560  cAMP-dependent protein kinase type II-beta regulatory subunit-like [KO:K04739]
120542852  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
120517381  prkar1aa; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) a [KO:K04739]
120531052  protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
120534000  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
120525034  solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
120531427  flotillin-2a isoform X1 [KO:K07192]
120539666  flotillin-1-like [KO:K07192]
120531298  SH2B adapter protein 2 isoform X1 [KO:K07193]
120516032  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
120535976  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
120523261  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
120531592  crk; adapter molecule crk isoform X1 [KO:K04438]
120540922  crkl; crk-like protein [KO:K04438]
120535056  rap guanine nucleotide exchange factor 1-like isoform X1 [KO:K06277]
120516498  rhoq; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
120541361  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
120543104  srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
120531370  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
120540759  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
120517955  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
120519331  LOW QUALITY PROTEIN: hexokinase HKDC1-like [KO:K00844] [EC:2.7.1.1]
120538866  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
120542585  hexokinase-2-like isoform X1 [KO:K00844] [EC:2.7.1.1]
120517281  hkdc1; LOW QUALITY PROTEIN: hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
120538964  gck; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
120527340  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
120543504  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
120540681  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a isoform X1 [KO:K07199]
120515229  5'-AMP-activated protein kinase subunit beta-2-like [KO:K07199]
120531235  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
120524852  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
120529860  prkag2a; 5'-AMP-activated protein kinase subunit gamma-2a isoform X1 [KO:K07200]
120524028  foxo1a; forkhead box protein O1-A [KO:K07201]
120527771  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
120531800  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
120517261  g6pc3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
120517264  glucose-6-phosphatase-like [KO:K01084] [EC:3.1.3.9]
120517265  g6pc1a.2; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
120517805  glucose-6-phosphatase-like [KO:K01084] [EC:3.1.3.9]
120517997  glucose-6-phosphatase-like [KO:K01084] [EC:3.1.3.9]
120532526  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
120532527  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
120515100  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
120525345  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
120530980  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
120518173  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
120538075  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
120531529  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
120532345  rps6; 40S ribosomal protein S6 [KO:K02991]
120538830  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
120525123  eukaryotic translation initiation factor 4E type 2-like isoform X1 [KO:K03259]
120533116  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
120516281  eif4e1c; eukaryotic translation initiation factor 4E family member 1c isoform X1 [KO:K03259]
120542457  eukaryotic translation initiation factor 4E-like [KO:K03259]
120536935  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
120536016  hamartin-like [KO:K07206]
120542319  tsc2; tuberin isoform X1 [KO:K07207]
120525161  rhebl1; ras homolog, mTORC1 binding like 1 isoform X1 [KO:K07208]
120529861  rheb; GTP-binding protein Rheb [KO:K07208]
120533795  bcl2-associated agonist of cell death-like [KO:K02158]
120528097  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
120537706  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
120532944  shc3; SHC-transforming protein 3 isoform X1 [KO:K17448]
120539955  SHC-transforming protein 1-like isoform X1 [KO:K17449]
120517145  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
120516982  son of sevenless homolog 1-like isoform X1 [KO:K03099]
120518289  sos2; son of sevenless homolog 2 [KO:K03099]
120523258  GTPase HRas [KO:K02833]
120534191  GTPase KRas isoform X1 [KO:K07827]
120542190  GTPase HRas-like [KO:K07827]
120526283  nras; GTPase NRas [KO:K07828]
120542924  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
120539426  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
120540276  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120541670  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120537759  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
120540631  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120536571  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120537911  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b isoform X1 [KO:K04372] [EC:2.7.11.1]
120542848  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
120542487  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
120525956  suppressor of cytokine signaling 2-like [KO:K04695]
120534018  socs2; suppressor of cytokine signaling 2 [KO:K04695]
120517676  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
120518961  socs4; suppressor of cytokine signaling 4 [KO:K04697]
120514295  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
120514292  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
120542011  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120527417  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120538805  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
120523937  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A isoform X1 [KO:K15909] [EC:3.1.3.86]
120537301  inppl1b; inositol polyphosphate phosphatase-like 1b [KO:K15909] [EC:3.1.3.86]
120540065  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
  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
psex00010  Glycolysis / Gluconeogenesis
psex00061  Fatty acid biosynthesis
psex00500  Starch and sucrose metabolism
psex04010  MAPK signaling pathway
psex04070  Phosphatidylinositol signaling system
psex04210  Apoptosis
KO pathway
ko04910   
LinkDB

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