KEGG   PATHWAY: msam04910
Entry
msam04910                   Pathway                                
Name
Insulin signaling pathway - Micropterus salmoides (largemouth bass)
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
msam04910  Insulin signaling pathway
msam04910

Organism
Micropterus salmoides (largemouth bass) [GN:msam]
Gene
119882013  [KO:K04365] [EC:2.7.11.1]
119882387  [KO:K00871] [EC:2.7.11.19]
119882554  rps6kb1b; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
119882692  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119882713  [KO:K01596] [EC:4.1.1.32]
119882844  flot2b; flotillin-2b isoform X1 [KO:K07192]
119882859  calm3a; calmodulin 3a (phosphorylase kinase, delta) isoform X1 [KO:K02183]
119883088  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
119883199  foxo1a; forkhead box protein O1-A [KO:K07201]
119883306  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
119883403  crk; adapter molecule crk isoform X1 [KO:K04438]
119883579  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
119883611  [KO:K07193]
119883760  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
119884117  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
119884553  [KO:K00844] [EC:2.7.1.1]
119885702  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
119885915  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
119886115  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
119886240  prkar2ab; protein kinase, cAMP-dependent, regulatory, type II, alpha, B [KO:K04739]
119886325  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119886334  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
119886349  [KO:K02183]
119886591  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
119886647  [KO:K07827]
119887256  [KO:K07200]
119888264  eif4ea; eukaryotic translation initiation factor 4E-1A isoform X1 [KO:K03259]
119888580  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
119888831  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
119888846  inppl1b; inositol polyphosphate phosphatase-like 1b isoform X1 [KO:K15909] [EC:3.1.3.86]
119888918  insb; preproinsulin b [KO:K04526]
119889675  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
119889719  socs4; suppressor of cytokine signaling 4 [KO:K04697]
119889880  [KO:K07189]
119889993  hkdc1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
119889994  [KO:K00844] [EC:2.7.1.1]
119890067  [KO:K02183]
119890282  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
119890292  phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
119890430  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
119890506  pde3b; LOW QUALITY PROTEIN: cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
119890775  [KO:K17449]
119891113  [KO:K00844] [EC:2.7.1.1]
119891161  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
119891193  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
119891295  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119891482  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
119891486  gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
119891493  [KO:K00844] [EC:2.7.1.1]
119891527  tsc1a; TSC complex subunit 1a isoform X1 [KO:K07206]
119891532  [KO:K06277]
119891547  [KO:K02649]
119891899  [KO:K07205]
119892122  fbp1a; fructose-1,6-bisphosphatase 1a [KO:K03841] [EC:3.1.3.11]
119892165  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
119892213  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
119892264  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
119892320  zgc:77112; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
119892400  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119892450  inpp5l; inositol polyphosphate-5-phosphatase A [KO:K01106] [EC:3.1.3.56]
119893118  [KO:K04739]
119893131  calml4b; calmodulin-like protein 4 [KO:K02183]
119893343  kras; GTPase KRas [KO:K07827]
119893575  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
119893612  map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
119893886  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
119894416  ppp1r3ab; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
119894945  ins; insulin [KO:K04526]
119894978  [KO:K04707] [EC:2.3.2.27]
119895022  [KO:K00844] [EC:2.7.1.1]
119895044  [KO:K04438]
119895081  [KO:K04456] [EC:2.7.11.1]
119895313  [KO:K07192]
119895400  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119895495  [KO:K04695]
119895496  [KO:K04695]
119895711  [KO:K07201]
119895784  cblb; E3 ubiquitin-protein ligase CBL-B-B isoform X1 [KO:K22517] [EC:2.3.2.27]
119895963  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
119896161  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
119896220  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119896388  [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119896511  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
119896812  [KO:K04456] [EC:2.7.11.1]
119897337  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
119897401  flot1b; flotillin-1b isoform X1 [KO:K07192]
119897457  [KO:K07200]
119897594  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
119897855  [KO:K00844] [EC:2.7.1.1]
119898122  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119898705  [KO:K07196]
119898768  [KO:K04694]
119898991  rps6; 40S ribosomal protein S6 [KO:K02991]
119899469  prkacab; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
119899493  tsc2; tuberin isoform X1 [KO:K07207]
119899739  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
119899805  [KO:K04688] [EC:2.7.11.1]
119899870  [KO:K03099]
119900224  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
119900335  [KO:K00922] [EC:2.7.1.153]
119900448  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
119900503  [KO:K02649]
119900632  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
119900689  [KO:K04527] [EC:2.7.10.1]
119900775  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
119900821  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
119900881  map2k2a; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
119901030  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
119901272  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
119901737  [KO:K07187]
119901826  rheb; GTP-binding protein Rheb [KO:K07208]
119901847  [KO:K05695] [EC:3.1.3.48]
119901871  insra; insulin receptor a isoform X1 [KO:K04527] [EC:2.7.10.1]
119901876  prkci; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
119902028  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
119902078  [KO:K07200]
119902234  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
119902325  [KO:K00922] [EC:2.7.1.153]
119902368  [KO:K02649]
119902696  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
119902876  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
119902893  prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
119902918  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
119903821  [KO:K02183]
119904210  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119904232  irs2b; insulin receptor substrate 2 [KO:K07187]
119904537  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b isoform X1 [KO:K07200]
119905054  elk1; LOW QUALITY PROTEIN: ETS domain-containing protein Elk-1 [KO:K04375]
119905212  [KO:K05696] [EC:3.1.3.48]
119905315  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
119905339  si:ch211-167b20.8; protein phosphatase 1 regulatory subunit 3A isoform X1 [KO:K07189]
119905617  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
119905717  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
119905755  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
119905919  [KO:K07203] [EC:2.7.11.1]
119905992  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
119907673  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
119907681  flot1a; flotillin-1a [KO:K07192]
119907925  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
119908532  [KO:K06269] [EC:3.1.3.16]
119909333  calm1b; calmodulin-1b [KO:K02183]
119909805  calm1a; calmodulin-1a [KO:K02183]
119910225  sos2; son of sevenless homolog 2 [KO:K03099]
119910231  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
119910321  [KO:K06269] [EC:3.1.3.16]
119910551  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119910882  eif4eb; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4eb [KO:K03259]
119911576  [KO:K07187]
119911743  badb; BCL2 associated agonist of cell death b isoform X1 [KO:K02158]
119911745  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
119911805  pygmb; phosphorylase, glycogen, muscle b [KO:K00688] [EC:2.4.1.1]
119911846  [KO:K06269] [EC:3.1.3.16]
119912349  [KO:K07191]
119912374  eif4e2rs1; eukaryotic translation initiation factor 4E family member 2 related sequence 1 [KO:K03259]
119912407  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119912463  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
119912584  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
119913394  [KO:K07189]
119914041  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119914123  rapgef1b; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1b [KO:K06277]
119914153  shc3; SHC-transforming protein 3 [KO:K17448]
119914204  tsc1b; TSC complex subunit 1b [KO:K07206]
119914247  crkl; crk-like protein [KO:K04438]
119914299  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
119914498  fbp1b; fructose-1,6-bisphosphatase 1b [KO:K03841] [EC:3.1.3.11]
119914607  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
119914828  [KO:K07205]
119915020  [KO:K17448]
119915031  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
119915070  si:dkey-242g16.2; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
119915391  g6pc3; LOW QUALITY PROTEIN: glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
119915534  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
119915538  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
119915567  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
119915573  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119915673  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
119915690  [KO:K07189]
119915799  [KO:K01084] [EC:3.1.3.9]
119915800  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
119915987  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
119916035  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
119916432  [KO:K04739]
119916947  [KO:K06086]
119916983  akt3a; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119917030  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119917210  [KO:K01106] [EC:3.1.3.56]
119917221  [KO:K07194]
119917346  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
119917366  eif4e1c; eukaryotic translation initiation factor 4E family member 1c isoform X1 [KO:K03259]
119917396  [KO:K02183]
119917992  braf; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
119918148  ppp1r3aa; uncharacterized protein ppp1r3aa isoform X1 [KO:K07189]
119918252  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
119918757  prkar1aa; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) a isoform X1 [KO:K04739]
119918811  [KO:K01084] [EC:3.1.3.9]
Compound
C00031  D-Glucose
C00369  Starch
C00575  3',5'-Cyclic AMP
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:14635525
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Seikagaku 75:1332-44 (2003)
Reference
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Insulin signalling.
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Reference
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Insulin signaling: GLUT4 vesicles exit via the exocyst.
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Curr Biol 13:R574-6 (2003)
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Reference
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Reference
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Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.
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Biochimie 87:99-109 (2005)
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Reference
PMID:9748166
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Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1.
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Science 281:2042-5 (1998)
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Reference
PMID:11742412
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Insulin signalling and the regulation of glucose and lipid metabolism.
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Nature 414:799-806 (2001)
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Reference
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Dysregulation of the TSC-mTOR pathway in human disease.
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Nat Genet 37:19-24 (2005)
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Reference
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The Akt of translational control.
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Oncogene 24:7426-34 (2005)
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Reference
PMID:10567225
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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.
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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
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  Title
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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Ceresa BP, Pessin JE.
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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
PMID:17344645
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SREBP-1c transcription factor and lipid homeostasis: clinical perspective.
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Horm Res 68:72-82 (2007)
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Reference
PMID:18291668
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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)
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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
msam00010  Glycolysis / Gluconeogenesis
msam00061  Fatty acid biosynthesis
msam00500  Starch and sucrose metabolism
msam04010  MAPK signaling pathway
msam04070  Phosphatidylinositol signaling system
msam04210  Apoptosis
KO pathway
ko04910   

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