KEGG   PATHWAY: mcoc04910
Entry
mcoc04910                   Pathway                                
Name
Insulin signaling pathway - Mastomys coucha (southern multimammate mouse)
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
mcoc04910  Insulin signaling pathway
mcoc04910

Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116101481  insulin-1 [KO:K04526]
116068825  Insr; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
116088647  Irs1; insulin receptor substrate 1 [KO:K16172]
116068902  Irs2; insulin receptor substrate 2 [KO:K07187]
116068604  insulin receptor substrate 1-like [KO:K17445]
116089083  Irs4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
116096465  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116083721  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116069491  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116095058  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116097037  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116073929  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116078189  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116085894  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116102200  Gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
116098429  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
116103326  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
116104637  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
116079614  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
116103783  Ppp1r3c; protein phosphatase 1 regulatory subunit 3C [KO:K07189]
116098590  Ppp1r3a; protein phosphatase 1 regulatory subunit 3A [KO:K07189]
116084525  Ppp1r3e; protein phosphatase 1 regulatory subunit 3E [KO:K07189]
116069148  Ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
116091512  Ppp1r3d; protein phosphatase 1 regulatory subunit 3D [KO:K07189]
116102143  Ppp1r3f; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453]
116103020  Phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
116068481  Phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
116087327  Phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
116069775  Phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
116090205  Phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
116102663  calmodulin-like [KO:K02183]
116101711  Calm3; calmodulin-3 [KO:K02183]
116082411  calmodulin-4 [KO:K02183]
116069997  calmodulin-like [KO:K02183]
116079808  Calm1; calmodulin-1 [KO:K02183]
116079993  Calm2; calmodulin-2 [KO:K02183]
116073523  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
116081777  calmodulin-like protein 3 [KO:K02183]
116103451  Pygm; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
116079987  Pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
116091133  Pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
116102827  Pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
116093928  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116069698  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116076681  Prkar1a; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
116068641  Prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
116079595  Prkar2b; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
116072077  Prkar2a; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739]
116101848  Lipe; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
116095810  Prkcz; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
116095037  Prkci; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
116079077  Slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
116074612  Flot1; flotillin-1 isoform X1 [KO:K07192]
116077409  Flot2; flotillin-2 isoform X1 [KO:K07192]
116068564  Sh2b2; SH2B adapter protein 2 isoform X1 [KO:K07193]
116103812  Sorbs1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
116073545  Cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
116085981  Cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
116085656  Crkl; crk-like protein [KO:K04438]
116078814  Crk; adapter molecule crk isoform X1 [KO:K04438]
116089919  Rapgef1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
116080782  Rhoq; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194]
116077163  Exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
116075019  Trip10; cdc42-interacting protein 4 isoform X1 [KO:K07196]
116077631  Srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
116076883  Acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116068218  Acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116079118  Fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
116093152  Pklr; pyruvate kinase PKLR [KO:K12406] [EC:2.7.1.40]
116099117  Hk2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
116074509  Hkdc1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
116075501  Hk1; hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
116081619  Hk3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
116068614  Gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
116096329  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
116083203  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
116093481  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
116068264  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
116097568  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
116088583  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
116079191  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
116094452  Foxo1; forkhead box protein O1 [KO:K07201]
116070819  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
116076828  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
116077838  G6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
116092006  G6pc2; LOW QUALITY PROTEIN: glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
116082329  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
116081758  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
116092572  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
116084755  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
116097015  Mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
116077504  Rptor; regulatory-associated protein of mTOR [KO:K07204]
116103319  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
116079205  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
116096209  Rps6; 40S ribosomal protein S6 [KO:K02991]
116069093  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
116093849  Eif4e; eukaryotic translation initiation factor 4E [KO:K03259]
116088713  Eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
116081759  Eif4e1b; eukaryotic translation initiation factor 4E type 1B [KO:K03259]
116089904  Tsc1; hamartin isoform X1 [KO:K07206]
116078562  Tsc2; tuberin isoform X1 [KO:K07207]
116097567  Rheb; GTP-binding protein Rheb [KO:K07208]
116103467  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
116093178  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
116076241  Shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
116081462  Shc3; SHC-transforming protein 3 [KO:K17448]
116090849  Shc4; SHC-transforming protein 4 [KO:K17449]
116076719  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
116080813  Sos1; son of sevenless homolog 1 [KO:K03099]
116080934  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116099791  Kras; GTPase KRas isoform X1 [KO:K07827]
116093530  Nras; GTPase NRas [KO:K07828]
116073820  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
116098774  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
116099433  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116073764  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116076013  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
116102969  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116073648  Mapk6; mitogen-activated protein kinase 6 [KO:K04371] [EC:2.7.11.24]
116085641  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116096445  Mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K04372] [EC:2.7.11.1]
116076077  Mknk2; MAP kinase-interacting serine/threonine-protein kinase 2 [KO:K04372] [EC:2.7.11.1]
116073994  Elk1; ETS domain-containing protein Elk-1 [KO:K04375]
116085165  Socs1; suppressor of cytokine signaling 1 isoform X1 [KO:K04694]
116075959  Socs2; suppressor of cytokine signaling 2 isoform X1 [KO:K04695]
116078408  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
116085200  Socs4; suppressor of cytokine signaling 4 [KO:K04697]
116091435  Ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
116096518  Ptprf; receptor-type tyrosine-protein phosphatase F isoform X1 [KO:K05695] [EC:3.1.3.48]
116085336  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116067982  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116076765  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116069014  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
116102675  Inppl1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
116103158  Inpp5a; inositol polyphosphate-5-phosphatase A isoform X1 [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
mcoc00010  Glycolysis / Gluconeogenesis
mcoc00061  Fatty acid biosynthesis
mcoc00500  Starch and sucrose metabolism
mcoc04010  MAPK signaling pathway
mcoc04070  Phosphatidylinositol signaling system
mcoc04210  Apoptosis
KO pathway
ko04910   
LinkDB

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