KEGG   PATHWAY: clum04910
Entry
clum04910                   Pathway                                
Name
Insulin signaling pathway - Cyclopterus lumpus (lumpfish)
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
clum04910  Insulin signaling pathway
clum04910

Organism
Cyclopterus lumpus (lumpfish) [GN:clum]
Gene
117742832  ins; insulin [KO:K04526]
117745971  insra; insulin receptor a isoform X1 [KO:K04527] [EC:2.7.10.1]
117729437  insrb; insulin receptor b isoform X1 [KO:K04527] [EC:2.7.10.1]
117742765  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
117747750  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
117750188  irs2b; insulin receptor substrate 2 [KO:K07187]
117741504  LOW QUALITY PROTEIN: insulin receptor substrate 2-like [KO:K07187]
117747932  insulin receptor substrate 2-B [KO:K07187]
117736025  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
117740185  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117746515  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
117729683  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
117729698  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
117746960  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
117732996  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117729144  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117746514  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
117741125  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117747650  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
117748707  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
117742397  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
117743684  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117732835  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117751396  akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117741120  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117750245  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117726209  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
117734505  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
117736119  serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
117749034  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
117727160  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
117751447  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
117734761  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
117747730  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
117731327  ppp1r3db; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
117736500  zgc:77112; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
117744411  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
117733528  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
117733540  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
117728598  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
117740976  ppp1r3b; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
117741971  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform-like [KO:K00871] [EC:2.7.11.19]
117748717  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
117748046  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
117749856  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
117750350  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
117726294  calml4a; calmodulin-like protein 4a [KO:K02183]
117743966  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
117727166  calm1b; calmodulin-1b [KO:K02183]
117751249  calm1a; calmodulin-1a isoform X1 [KO:K02183]
117741237  calm3a; calmodulin 3a (phosphorylase kinase, delta) isoform X1 [KO:K02183]
117730495  LOW QUALITY PROTEIN: calglandulin-like [KO:K02183]
117742594  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
117751098  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
117747771  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
117749025  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
117729101  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117746316  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
117729746  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
117734821  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a [KO:K04345] [EC:2.7.11.11]
117730690  prkar2ab; protein kinase, cAMP-dependent, regulatory, type II, alpha, B [KO:K04739]
117748532  cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
117732414  cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
117732998  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
117735653  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
117735681  prkar1aa; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) a [KO:K04739]
117739107  lipea; lipase, hormone-sensitive a isoform X1 [KO:K07188] [EC:3.1.1.79]
117745886  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
117733748  prkcz; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
117747046  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
117747866  solute carrier family 2, facilitated glucose transporter member 4-like isoform X1 [KO:K07191]
117743052  flotillin-2a isoform X1 [KO:K07192]
117739124  flot1a; flotillin-1a [KO:K07192]
117745470  flot1b; flotillin-1b [KO:K07192]
117728117  flotillin-2 [KO:K07192]
117741478  SH2B adapter protein 2 [KO:K07193]
117744065  sorbin and SH3 domain-containing protein 1 [KO:K06086]
117741864  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
117743080  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
117742422  cblb; E3 ubiquitin-protein ligase CBL-B-B isoform X1 [KO:K22517] [EC:2.3.2.27]
117741967  crk; adapter molecule crk [KO:K04438]
117742730  adapter molecule crk-like [KO:K04438]
117740248  crkl; crk-like protein [KO:K04438]
117736307  rapgef1a; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1 [KO:K06277]
117744324  rho-related GTP-binding protein RhoQ [KO:K07194]
117748467  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
117732597  cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
117735322  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
117735396  srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
117742271  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117736297  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117748403  fasn; fatty acid synthase isoform X1 [KO:K00665] [EC:2.3.1.85]
117736067  hk2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
117743134  hexokinase-2-like [KO:K00844] [EC:2.7.1.1]
117732476  hexokinase-1-like isoform X1 [KO:K00844] [EC:2.7.1.1]
117747706  hexokinase HKDC1-like isoform X1 [KO:K00844] [EC:2.7.1.1]
117747721  hexokinase-1-like [KO:K00844] [EC:2.7.1.1]
117736413  LOW QUALITY PROTEIN: hexokinase-4-like [KO:K12407] [EC:2.7.1.2]
117740334  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
117729339  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
117736940  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
117746256  5'-AMP-activated protein kinase subunit beta-2-like isoform X1 [KO:K07199]
117740813  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
117731160  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
117749405  5'-AMP-activated protein kinase subunit gamma-1-like [KO:K07200]
117743747  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
117750339  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b [KO:K07200]
117746088  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
117742401  forkhead box protein O1-A-like [KO:K07201]
117741081  foxo1a; forkhead box protein O1-A [KO:K07201]
117748189  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
117748521  g6pc3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
117749127  g6pca.2; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
117749128  g6pca.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
117735801  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
117735802  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
117740493  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
117749394  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
117731497  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
117733186  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
117732125  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
117742379  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
117729225  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
117741467  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
117736225  rps6; 40S ribosomal protein S6 [KO:K02991]
117736949  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
117740409  eukaryotic translation initiation factor 4E-binding protein 1-like isoform X1 [KO:K07205]
117744054  eif4e1c; eukaryotic translation initiation factor 4E family member 1c [KO:K03259]
117738022  eukaryotic translation initiation factor 4E-1A-like [KO:K03259]
117746275  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
117751566  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
117748000  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 [KO:K03259]
117736924  tsc1a; TSC complex subunit 1a [KO:K07206]
117740320  tsc1b; TSC complex subunit 1b isoform X1 [KO:K07206]
117729575  tsc2; tuberin isoform X1 [KO:K07207]
117731173  rhebl1; ras homolog, mTORC1 binding like 1 isoform X1 [KO:K07208]
117747098  rheb; GTP-binding protein Rheb [KO:K07208]
117747774  badb; BCL2 associated agonist of cell death b [KO:K02158]
117745760  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
117729725  shc2; SHC-transforming protein 2 [KO:K17447]
117740595  shc3; SHC-transforming protein 3 [KO:K17448]
117747334  SHC-transforming protein 4-like [KO:K17449]
117731203  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
117734621  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
117725278  sos2; son of sevenless homolog 2 [KO:K03099]
117729085  son of sevenless homolog 1-like [KO:K03099]
117732119  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
117731941  kras; GTPase KRas isoform X1 [KO:K07827]
117735017  zgc:55558; GTPase HRas [KO:K07827]
117735957  araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
117725940  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
117733950  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
117732847  map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
117746647  map2k2b; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
117729985  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
117736137  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117735491  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117729122  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
117729226  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
117733046  elk1; ETS domain-containing protein Elk-3 [KO:K04375]
117738860  socs1b; suppressor of cytokine signaling 1b [KO:K04694]
117735604  socs1a; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1a [KO:K04694]
117726021  socs2; suppressor of cytokine signaling 2 [KO:K04695]
117748644  suppressor of cytokine signaling 3-like [KO:K04696]
117734887  socs3a; LOW QUALITY PROTEIN: suppressor of cytokine signaling 3a [KO:K04696]
117728837  socs4; suppressor of cytokine signaling 4 [KO:K04697]
117733088  tyrosine-protein phosphatase non-receptor type 1-like [KO:K05696] [EC:3.1.3.48]
117745969  receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
117729457  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
117748413  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117737372  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
117743832  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117740127  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
117736821  ikbkb; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
117737654  inppl1b; inositol polyphosphate phosphatase-like 1b [KO:K15909] [EC:3.1.3.86]
117741329  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A isoform X1 [KO:K15909] [EC:3.1.3.86]
117743862  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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Insulin regulation of the Ras activation/inactivation cycle.
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Reference
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Reference
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Reference
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  Journal
Adv Enzyme Regul 43:15-28 (2003)
DOI:10.1016/S0065-2571(02)00043-2
Related
pathway
clum00010  Glycolysis / Gluconeogenesis
clum00061  Fatty acid biosynthesis
clum00500  Starch and sucrose metabolism
clum04010  MAPK signaling pathway
clum04070  Phosphatidylinositol signaling system
clum04210  Apoptosis
KO pathway
ko04910   
LinkDB

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