KEGG   PATHWAY: cbai04910
Entry
cbai04910                   Pathway                                
Name
Insulin signaling pathway - Camelus bactrianus (Bactrian camel)
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
cbai04910  Insulin signaling pathway
cbai04910

Organism
Camelus bactrianus (Bactrian camel) [GN:cbai]
Gene
105078270  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
105064075  IRS1; insulin receptor substrate 1 [KO:K16172]
105078567  uncharacterized protein LOC105078567 [KO:K17445]
105061987  IRS4; insulin receptor substrate 4 [KO:K17446]
105082679  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105064416  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
105065663  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105063312  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105071167  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105066839  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105064838  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105079975  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105083596  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105062855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105081598  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105062281  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
105062760  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
105080605  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
105063807  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
105070330  PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
105081834  PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
105073777  LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 3D-like [KO:K07189]
105063159  PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
105071793  PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
105067635  PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
105079419  PPP1R3F; protein phosphatase 1 regulatory subunit 3F [KO:K17453]
105082757  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
105082793  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
105083671  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
105068660  PHKA2; LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
105065140  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
105074723  calmodulin-like [KO:K02183]
105079857  CALM1; calmodulin [KO:K02183]
105079032  CALM2; calmodulin [KO:K02183]
105062547  CALM3; calmodulin [KO:K02183]
105069522  CALML4; calmodulin-like protein 4 [KO:K02183]
105071194  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105083188  PYGB; LOW QUALITY PROTEIN: glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
105078429  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
105070647  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
105076796  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
105075498  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105068302  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105080280  PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
105077833  PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
105062423  PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
105063928  PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
105062447  LIPE; LOW QUALITY PROTEIN: hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
105071048  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
105066689  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
105077487  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
105074101  FLOT1; flotillin-1 [KO:K07192]
105071555  FLOT2; flotillin-2 [KO:K07192]
105067517  SH2B2; SH2B adapter protein 2 [KO:K07193]
105081805  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
105067865  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
105080142  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
105070566  CRKL; crk-like protein [KO:K04438]
105071519  CRK; adapter molecule crk [KO:K04438]
105069710  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
105079025  RHOQ; rho-related GTP-binding protein RhoQ [KO:K07194]
105065631  EXOC7; exocyst complex component 7 [KO:K07195]
105078265  TRIP10; cdc42-interacting protein 4 [KO:K07196]
105082523  SREBF1; LOW QUALITY PROTEIN: sterol regulatory element-binding protein 1 [KO:K07197]
105064304  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
105075668  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
105065535  FASN; LOW QUALITY PROTEIN: fatty acid synthase [KO:K00665] [EC:2.3.1.85]
105068153  PKLR; pyruvate kinase PKLR isoform X1 [KO:K12406] [EC:2.7.1.40]
105067752  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
105062047  HK3; hexokinase-3 [KO:K00844] [EC:2.7.1.1]
105066353  HK1; LOW QUALITY PROTEIN: hexokinase-1 [KO:K00844] [EC:2.7.1.1]
105066355  HKDC1; LOW QUALITY PROTEIN: putative hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
105080693  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
105070805  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
105071667  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
105080553  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
105079157  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
105076196  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
105064024  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
105067027  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
105066187  FOXO1; forkhead box protein O1 [KO:K07201]
105075295  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
105080088  G6PC; LOW QUALITY PROTEIN: glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
105081978  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
105072558  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
105078805  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
105078806  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
105068796  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
105071815  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
105070974  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105065574  RPTOR; regulatory-associated protein of mTOR [KO:K07204]
105070333  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
105065845  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105077284  40S ribosomal protein S6-like [KO:K02991]
105061888  RPS6; 40S ribosomal protein S6 [KO:K02991]
105067888  EIF4E; eukaryotic translation initiation factor 4E [KO:K03259]
105062090  EIF4E1B; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E type 1B [KO:K03259]
105063584  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
105069721  TSC1; hamartin [KO:K07206]
105064853  TSC2; tuberin [KO:K07207]
105067026  RHEB; GTP-binding protein Rheb [KO:K07208]
105070634  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
105068173  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105078342  SHC2; SHC-transforming protein 2 [KO:K17447]
105065419  SHC3; SHC-transforming protein 3 [KO:K17448]
105077007  SHC4; SHC-transforming protein 4 [KO:K17449]
105065653  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105078489  SOS2; son of sevenless homolog 2 [KO:K03099]
105078987  SOS1; son of sevenless homolog 1 [KO:K03099]
105069943  HRAS; GTPase HRas isoform X1 [KO:K02833]
105062297  KRAS; GTPase KRas [KO:K07827]
105079555  NRAS; GTPase NRas [KO:K07828]
105079376  ARAF; LOW QUALITY PROTEIN: serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105063019  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
105067475  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105069422  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105078209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105082839  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105069349  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105078155  MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
105065770  MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
105079378  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
105074255  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
105074996  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
105065593  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
105074596  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
105071851  PTPN1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
105072712  PTPRF; receptor-type tyrosine-protein phosphatase F [KO:K05695] [EC:3.1.3.48]
105075609  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105077723  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105062001  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105071245  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105083289  INPPL1; LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909] [EC:3.1.3.86]
105067057  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
cbai00010  Glycolysis / Gluconeogenesis
cbai00061  Fatty acid biosynthesis
cbai00500  Starch and sucrose metabolism
cbai04010  MAPK signaling pathway
cbai04070  Phosphatidylinositol signaling system
cbai04210  Apoptosis
KO pathway
ko04910   
LinkDB

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