KEGG   PATHWAY: cpea04910
Entry
cpea04910                   Pathway                                
Name
Insulin signaling pathway - Chaetura pelagica (chimney swift)
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
cpea04910  Insulin signaling pathway
cpea04910

Organism
Chaetura pelagica (chimney swift) [GN:cpea]
Gene
104394306  insulin [KO:K04526]
104388871  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
104392276  IRS1; insulin receptor substrate 1 [KO:K16172]
104388287  IRS4; insulin receptor substrate 4 [KO:K07187]
104395652  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104396688  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104388868  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104390114  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104395385  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104395456  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104393099  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
104394936  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104387153  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104389283  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
104386767  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
104389431  PPP1CC; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
104395247  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
104392017  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
104384848  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
104389605  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
104394660  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
104390830  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
104387181  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
104384896  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
104388264  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
104388576  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
104393927  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
104394189  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
104395269  CALM2; calmodulin [KO:K02183]
104391078  CALML3; calmodulin-like protein 3 [KO:K02183]
104386526  CALML4; calmodulin-like protein 4 [KO:K02183]
104394455  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
104388675  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
104385783  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
104396726  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104394279  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
104388203  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
104393320  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
104398221  cAMP-dependent protein kinase type II-alpha regulatory subunit-like [KO:K04739]
104393745  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
104395491  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
104396766  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
104387852  LOW QUALITY PROTEIN: flotillin-2-like [KO:K07192]
104396232  SH2B2; SH2B adapter protein 2 [KO:K07193]
104391474  SORBS1; sorbin and SH3 domain-containing protein 1 [KO:K06086]
104386069  CBL; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
104384962  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
104384916  CRK; adapter molecule crk [KO:K04438]
104395117  CRKL; crk-like protein [KO:K04438]
104389831  RAPGEF1; rap guanine nucleotide exchange factor 1 [KO:K06277]
104395273  RHOQ; LOW QUALITY PROTEIN: rho-related GTP-binding protein RhoQ [KO:K07194]
104394060  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
104398890  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
104388037  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
104398526  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
104390242  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
104386284  HKDC1; putative hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
104386305  HK1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
104392672  HK3; hexokinase-3 [KO:K00844] [EC:2.7.1.1]
104391564  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
104385189  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
104398615  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
104395156  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
104390688  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
104396184  PRKAG2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
104387333  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
104389374  FOXO1; forkhead box protein O1 [KO:K07201]
104397341  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
104385646  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
104385861  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
104387371  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
104397255  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
104397268  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
104389616  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
104395443  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
104398534  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
104398903  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
104398378  RPS6; 40S ribosomal protein S6 [KO:K02991]
104384872  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
104391029  EIF4E2; eukaryotic translation initiation factor 4E type 2 [KO:K03259]
104392674  EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
104393658  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
104389825  TSC1; hamartin isoform X1 [KO:K07206]
104393110  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
104396200  RHEB; GTP-binding protein Rheb [KO:K07208]
104387520  SHC1; SHC-transforming protein 1 [KO:K06279]
104392436  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
104387006  SHC3; SHC-transforming protein 3 [KO:K17448]
104386019  SHC4; SHC-transforming protein 4 [KO:K17449]
104393177  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
104394717  SOS2; son of sevenless homolog 2 [KO:K03099]
104398553  SOS1; son of sevenless homolog 1 [KO:K03099]
104387643  HRAS; GTPase HRas [KO:K02833]
104386764  KRAS; GTPase KRas isoform X1 [KO:K07827]
104392909  NRAS; GTPase NRas [KO:K07828]
104396045  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
104398706  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
104386653  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104391569  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
104388745  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104396683  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
104388067  MKNK2; LOW QUALITY PROTEIN: MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
104393688  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
104397984  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
104398552  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
104387672  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
104389639  PTPN1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
104396709  PTPRF; receptor-type tyrosine-protein phosphatase F [KO:K05695] [EC:3.1.3.48]
104385199  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104391113  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104386555  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104384891  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104387830  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909] [EC:3.1.3.86]
104388659  INPP5A; type I inositol 1,4,5-trisphosphate 5-phosphatase [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
cpea00010  Glycolysis / Gluconeogenesis
cpea00061  Fatty acid biosynthesis
cpea00500  Starch and sucrose metabolism
cpea04010  MAPK signaling pathway
cpea04070  Phosphatidylinositol signaling system
cpea04210  Apoptosis
KO pathway
ko04910   
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