KEGG   PATHWAY: emac04910
Entry
emac04910                   Pathway                                
Name
Insulin signaling pathway - Eleginops maclovinus (Patagonian blennie)
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
emac04910  Insulin signaling pathway
emac04910

Organism
Eleginops maclovinus (Patagonian blennie) [GN:emac]
Gene
134872400  insulin-like [KO:K04526]
134860340  insb; preproinsulin b [KO:K04526]
134865781  insra; insulin receptor a [KO:K04527] [EC:2.7.10.1]
134870225  insrb; LOW QUALITY PROTEIN: insulin receptor b [KO:K04527] [EC:2.7.10.1]
134871912  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
134876328  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
134860795  insulin receptor substrate 2-like isoform X1 [KO:K07187]
134867157  irs2b; LOW QUALITY PROTEIN: insulin receptor substrate 2 [KO:K07187]
134875976  insulin receptor substrate 2-B [KO:K07187]
134869270  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
134865729  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
134865816  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
134869506  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
134868191  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
134873278  phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
134863333  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
134869576  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
134866128  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
134880313  pik3cb; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
134870788  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
134865040  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
134871875  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
134871879  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
134880032  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
134881467  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
134866892  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
134877917  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
134879235  gys2; LOW QUALITY PROTEIN: glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
134870589  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
134877778  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
134873899  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A isoform X1 [KO:K06269] [EC:3.1.3.16]
134875912  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
134881896  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
134876668  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
134868649  protein phosphatase 1 regulatory subunit 3B-like [KO:K07189]
134858946  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
134866003  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
134871408  protein phosphatase 1 regulatory subunit 3C-B-like isoform X1 [KO:K07189]
134871787  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K07189]
134862883  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
134879547  ppp1r3aa; uncharacterized protein ppp1r3aa isoform X1 [KO:K07189]
134874076  ppp1r3c2b; protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
134882449  ppp1r3db; protein phosphatase 1, regulatory subunit 3Db [KO:K07189]
134870543  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
134880704  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform-like [KO:K00871] [EC:2.7.11.19]
134863058  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
134863778  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
134875941  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
134863316  calml4a; calmodulin-like protein 4a [KO:K02183]
134858627  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
134879999  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
134881853  calmodulin-1-like isoform X1 [KO:K02183]
134876663  calm1b; calmodulin-1b [KO:K02183]
134883161  calml4b; calmodulin-like protein 4 [KO:K02183]
134872461  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
134875846  pygmb; phosphorylase, glycogen, muscle b [KO:K00688] [EC:2.4.1.1]
134882054  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
134862708  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
134869312  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
134864525  prkacab; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
134866033  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
134877550  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
134866398  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
134871342  cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
134878337  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
134882511  prkar2ab; protein kinase, cAMP-dependent, regulatory, type II, alpha, B isoform X1 [KO:K04739]
134877575  prkar1aa; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) a [KO:K04739]
134861718  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
134875241  lipea; lipase, hormone-sensitive a isoform X1 [KO:K07188] [EC:3.1.1.79]
134870463  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
134865550  prkci; LOW QUALITY PROTEIN: protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
134875881  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
134861273  flot1b; flotillin-1b [KO:K07192]
134872096  flotillin-2a isoform X1 [KO:K07192]
134880205  flotillin-2 isoform X1 [KO:K07192]
134875410  flot1a; flotillin-1a isoform X1 [KO:K07192]
134880135  SH2B adapter protein 2 [KO:K07193]
134858581  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
134872179  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
134880721  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
134872063  cblb; E3 ubiquitin-protein ligase CBL-B-B [KO:K22517] [EC:2.3.2.27]
134868485  crkl; crk-like protein [KO:K04438]
134872004  adapter molecule crk-like [KO:K04438]
134879932  LOW QUALITY PROTEIN: adapter molecule crk-like [KO:K04438]
134868251  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X1 [KO:K06277]
134873710  rapgef1a; rap guanine nucleotide exchange factor 1 [KO:K06277]
134858644  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
134870845  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
134865271  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
134878208  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
134878096  srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
134871948  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
134873256  acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
134870650  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
134863454  hexokinase HKDC1-like [KO:K00844] [EC:2.7.1.1]
134863455  hk1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
134864197  hexokinase-1 [KO:K00844] [EC:2.7.1.1]
134871815  LOW QUALITY PROTEIN: hexokinase-4-like [KO:K00844] [EC:2.7.1.1]
134873568  hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
134873291  gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
134869926  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
134868340  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
134868838  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
134865542  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
134873998  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b isoform X1 [KO:K07199]
134858116  5'-AMP-activated protein kinase subunit gamma-2-like [KO:K07200]
134865943  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
134860870  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
134867887  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b [KO:K07200]
134883041  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
134872324  forkhead box protein O1-A-like [KO:K07201]
134880551  foxo1a; forkhead box protein O1-A [KO:K07201]
134875964  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
134871201  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
134871330  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
134871332  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
134868981  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
134873517  fbp1a; fructose-1,6-bisphosphatase 1a [KO:K03841] [EC:3.1.3.11]
134873519  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
134883858  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
134883357  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
134867502  mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
134864950  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
134864249  ribosomal protein S6 kinase beta-2-like isoform X1 [KO:K04688] [EC:2.7.11.1]
134871617  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
134880017  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
134865081  rps6; 40S ribosomal protein S6 [KO:K02991]
134867984  eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
134873448  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
134858603  eif4e1c; eukaryotic translation initiation factor 4E family member 1c [KO:K03259]
134859373  eukaryotic translation initiation factor 4E-1A [KO:K03259]
134866266  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
134880959  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
134875693  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 isoform X1 [KO:K03259]
134868553  tsc1b; TSC complex subunit 1b isoform X1 [KO:K07206]
134873741  tsc1a; TSC complex subunit 1a isoform X1 [KO:K07206]
134864423  tsc2; tuberin isoform X1 [KO:K07207]
134865524  rheb; GTP-binding protein Rheb [KO:K07208]
134882495  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
134875663  badb; BCL2 associated agonist of cell death b isoform X1 [KO:K02158]
134861829  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
134869118  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
134867979  shc3; SHC-transforming protein 3 [KO:K17448]
134863773  SHC-transforming protein 1-like isoform X1 [KO:K17449]
134878303  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
134862968  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
134881897  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
134876142  hrasb; HRas proto-oncogene, GTPase b isoform X1 [KO:K02833]
134859177  kras; GTPase KRas isoform X1 [KO:K07827]
134877937  zgc:55558; GTPase KRas [KO:K07827]
134873719  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
134879164  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
134865609  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
134879440  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
134869745  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
134866187  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
134877926  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
134873272  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
134869471  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
134869580  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
134866294  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
134864759  suppressor of cytokine signaling 1-like [KO:K04694]
134878623  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
134879034  socs2; suppressor of cytokine signaling 2 [KO:K04695]
134870833  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
134878037  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
134863738  socs4; suppressor of cytokine signaling 4 [KO:K04697]
134862219  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
134865608  receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
134869453  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
134868533  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
134859047  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
134859865  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
134870548  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
134873220  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
134859947  inppl1b; inositol polyphosphate phosphatase-like 1b isoform X1 [KO:K15909] [EC:3.1.3.86]
134880326  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A isoform X1 [KO:K15909] [EC:3.1.3.86]
134858611  inositol polyphosphate-5-phosphatase A isoform X1 [KO:K01106] [EC:3.1.3.56]
134873876  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
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Reference
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Reference
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Role of binding proteins to IRS-1 in insulin signalling.
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Reference
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Reference
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Horm Res 68:72-82 (2007)
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Reference
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  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
emac00010  Glycolysis / Gluconeogenesis
emac00061  Fatty acid biosynthesis
emac00500  Starch and sucrose metabolism
emac04010  MAPK signaling pathway
emac04070  Phosphatidylinositol signaling system
emac04210  Apoptosis
KO pathway
ko04910   
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