KEGG   PATHWAY: ccri04910
Entry
ccri04910                   Pathway                                
Name
Insulin signaling pathway - Cariama cristata (Red-legged seriema)
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
ccri04910  Insulin signaling pathway
ccri04910

Organism
Cariama cristata (Red-legged seriema) [GN:ccri]
Gene
104163519  INS; insulin [KO:K04526]
104160448  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
104164059  IRS1; LOW QUALITY PROTEIN: insulin receptor substrate 1 [KO:K16172]
104157181  IRS2; insulin receptor substrate 2 [KO:K07187]
104169467  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104158448  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104160278  PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104155370  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104169388  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104160022  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104161988  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
104168903  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104165413  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104163168  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104168294  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
104166658  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
104158660  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
104164474  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
104156675  protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
104158603  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
104158752  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
104166774  protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
104159620  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
104166197  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
104158414  LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit beta-like [KO:K07190]
104154584  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
104167546  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
104157977  CALML4; calmodulin-like protein 4 [KO:K02183]
104162712  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
104166475  calmodulin, striated muscle [KO:K02183]
104160048  calmodulin-like [KO:K02183]
104156881  calmodulin-like [KO:K02183]
104162564  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
104167046  glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
104159956  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
104167339  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104155480  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
104156167  cAMP-dependent protein kinase type I-alpha regulatory subunit-like [KO:K04739]
104163292  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
104155508  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
104168954  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
104160600  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
104159734  FLOT2; flotillin-2 isoform X1 [KO:K07192]
104159591  LOW QUALITY PROTEIN: SH2B adapter protein 2-like [KO:K07193]
104168232  SORBS1; sorbin and SH3 domain-containing protein 1 [KO:K06086]
104166982  CBL; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
104157926  CBLB; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
104158876  CRK; adapter molecule crk [KO:K04438]
104163755  CRKL; crk-like protein [KO:K04438]
104166620  rap guanine nucleotide exchange factor 1-like [KO:K06277]
104155290  rap guanine nucleotide exchange factor 1-like [KO:K06277]
104166745  RHOQ; rho-related GTP-binding protein RhoQ [KO:K07194]
104166200  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
104169304  LOW QUALITY PROTEIN: acetyl-CoA carboxylase-like [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
104164563  ACACB; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
104159587  FASN; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
104169031  HK1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
104169489  LOW QUALITY PROTEIN: hexokinase-3-like [KO:K00844] [EC:2.7.1.1]
104158540  HKDC1; putative hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
104167699  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
104166344  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
104161253  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
104162070  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
104168985  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
104156998  PRKAB1; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
104167286  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
104167266  FOXO1; forkhead box protein O1 [KO:K07201]
104167572  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
104166331  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
104155576  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
104156088  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
104168588  LOW QUALITY PROTEIN: phosphoenolpyruvate carboxykinase [GTP], mitochondrial-like [KO:K01596] [EC:4.1.1.32]
104167522  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
104163472  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
104168339  RPTOR; LOW QUALITY PROTEIN: regulatory-associated protein of mTOR [KO:K07204]
104155331  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
104161425  RPS6; 40S ribosomal protein S6 [KO:K02991]
104157098  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
104161889  EIF4E2; eukaryotic translation initiation factor 4E type 2 [KO:K03259]
104156405  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
104163585  eukaryotic translation initiation factor 4E-like [KO:K03259]
104165372  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
104161623  TSC2; tuberin [KO:K07207]
104162225  RHEB; GTP-binding protein Rheb [KO:K07208]
104169019  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
104158850  SHC3; SHC-transforming protein 3 [KO:K17448]
104161587  SHC4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
104163675  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
104169016  SOS2; son of sevenless homolog 2 [KO:K03099]
104161965  SOS1; son of sevenless homolog 1 [KO:K03099]
104158389  HRAS; GTPase HRas [KO:K02833]
104156747  KRAS; GTPase KRas isoform X1 [KO:K07827]
104156287  NRAS; GTPase NRas [KO:K07828]
104168469  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
104158886  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
104158875  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104154633  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104162895  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104154565  MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
104160488  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
104157168  SOCS2; LOW QUALITY PROTEIN: suppressor of cytokine signaling 2 [KO:K04695]
104167126  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
104159301  PTPN1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
104161754  PTPRF; receptor-type tyrosine-protein phosphatase F [KO:K05695] [EC:3.1.3.48]
104168638  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104165937  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104164462  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104155069  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
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
ccri00010  Glycolysis / Gluconeogenesis
ccri00061  Fatty acid biosynthesis
ccri00500  Starch and sucrose metabolism
ccri04010  MAPK signaling pathway
ccri04070  Phosphatidylinositol signaling system
ccri04210  Apoptosis
KO pathway
ko04910   
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