KEGG   PATHWAY: lrj04910
Entry
lrj04910                    Pathway                                
Name
Insulin signaling pathway - Lethenteron reissneri (Far Eastern brook lamprey)
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
lrj04910  Insulin signaling pathway
lrj04910

Organism
Lethenteron reissneri (Far Eastern brook lamprey) [GN:lrj]
Gene
133347390  insulin-like [KO:K04526]
133355163  insulin-like growth factor 1 receptor [KO:K04527] [EC:2.7.10.1]
133354143  LOW QUALITY PROTEIN: insulin-like growth factor 1 receptor [KO:K04527] [EC:2.7.10.1]
133353767  insulin receptor substrate 1-B-like [KO:K16172]
133357147  insulin receptor substrate 1-B-like isoform X1 [KO:K07187]
133352049  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
133351084  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
133347045  PDPK1; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
133347062  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
133356301  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
133358608  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
133350326  glycogen [starch] synthase, liver-like [KO:K00693] [EC:2.4.1.11]
133359921  glycogen [starch] synthase, muscle-like [KO:K00693] [EC:2.4.1.11]
133352687  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
133347017  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
133348396  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
133342219  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
133343491  protein phosphatase 1 regulatory subunit 3C-B-like isoform X1 [KO:K07189]
133340274  protein phosphatase 1 regulatory subunit 3E-like isoform X1 [KO:K07189]
133354952  protein phosphatase 1 regulatory subunit 3D-like isoform X1 [KO:K07189]
133348871  PHKG1; LOW QUALITY PROTEIN: phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
133357689  LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, liver isoform-like [KO:K07190]
133340459  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
133354795  phosphorylase b kinase regulatory subunit beta-like [KO:K07190]
133352568  calmodulin-1-like [KO:K02183]
133362997  calmodulin-alpha-like [KO:K02183]
133341316  CALM1; calmodulin-1 [KO:K02183]
133342379  CALM2; calmodulin-2 isoform X1 [KO:K02183]
133352557  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
133347243  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
133341433  glycogen phosphorylase, brain form-like [KO:K00688] [EC:2.4.1.1]
133350602  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
133350622  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
133359043  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
133358870  cAMP-dependent protein kinase type I-alpha regulatory subunit-like [KO:K04739]
133346435  cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
133347837  cAMP-dependent protein kinase type I-beta regulatory subunit-like [KO:K04739]
133347919  cAMP-dependent protein kinase type I-beta regulatory subunit-like [KO:K04739]
133349437  cAMP-dependent protein kinase type II-alpha regulatory subunit-like [KO:K04739]
133355636  cAMP-dependent protein kinase type II-alpha regulatory subunit-like isoform X1 [KO:K04739]
133351181  protein kinase C iota type-like isoform X1 [KO:K06069] [EC:2.7.11.13]
133352496  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
133342015  FLOT1; flotillin-1 [KO:K07192]
133348901  FLOT2; flotillin-2 isoform X1 [KO:K07192]
133358470  E3 ubiquitin-protein ligase CBL-like isoform X1 [KO:K22517] [EC:2.3.2.27]
133358472  E3 ubiquitin-protein ligase CBL-B-like [KO:K22517] [EC:2.3.2.27]
133341985  E3 ubiquitin-protein ligase CBL-B-B-like [KO:K22517] [EC:2.3.2.27]
133343934  crk-like protein [KO:K04438]
133348530  CRKL; crk-like protein [KO:K04438]
133348464  uncharacterized protein LOC133348464 [KO:K06277]
133354714  LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1-like [KO:K06277]
133360737  RHOJ; rho-related GTP-binding protein RhoJ [KO:K07194]
133353501  exocyst complex component 7-like [KO:K07195]
133354981  EXOC7; exocyst complex component 7 isoform X1 [KO:K07195]
133353642  SREBF1; LOW QUALITY PROTEIN: sterol regulatory element-binding protein 1 [KO:K07197]
133348511  acetyl-CoA carboxylase-like isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
133348916  ACACA; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
133346008  FASN; LOW QUALITY PROTEIN: fatty acid synthase [KO:K00665] [EC:2.3.1.85]
133343558  hexokinase-2-like isoform X1 [KO:K00844] [EC:2.7.1.1]
133340363  hexokinase-1-like [KO:K00844] [EC:2.7.1.1]
133343469  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
133359123  5'-AMP-activated protein kinase catalytic subunit alpha-2-like [KO:K07198] [EC:2.7.11.31]
133359124  5'-AMP-activated protein kinase catalytic subunit alpha-2-like [KO:K07198] [EC:2.7.11.31]
133345002  5'-AMP-activated protein kinase subunit gamma-1-like isoform X1 [KO:K07200]
133345944  5'-AMP-activated protein kinase subunit gamma-2-like [KO:K07200]
133345136  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
133345279  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
133358373  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
133343699  fructose-1,6-bisphosphatase isozyme 2-like [KO:K03841] [EC:3.1.3.11]
133354302  LOW QUALITY PROTEIN: fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
133354919  phosphoenolpyruvate carboxykinase [GTP], mitochondrial-like [KO:K01596] [EC:4.1.1.32]
133348084  RPTOR; LOW QUALITY PROTEIN: regulatory-associated protein of mTOR [KO:K07204]
133354102  RPS6; small ribosomal subunit protein eS6 [KO:K02991]
133339278  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
133350519  eukaryotic translation initiation factor 4E-like [KO:K03259]
133357279  EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
133361294  eukaryotic translation initiation factor 4E-1A-like isoform X1 [KO:K03259]
133362750  eukaryotic translation initiation factor 4E-like [KO:K03259]
133362756  eukaryotic translation initiation factor 4E-like [KO:K03259]
133354389  LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E-like [KO:K03259]
133341737  TSC1; hamartin isoform X1 [KO:K07206]
133347575  TSC2; tuberin [KO:K07207]
133344654  GTP-binding protein Rheb-like [KO:K07208]
133345003  GTP-binding protein Rheb-like [KO:K07208]
133358400  GTP-binding protein Rheb-like [KO:K07208]
133354191  SHC-transforming protein 1-like [KO:K06279]
133355129  SHC1; SHC-transforming protein 1 [KO:K06279]
133340992  growth factor receptor-bound protein 2 [KO:K04364]
133348060  growth factor receptor-bound protein 2-like [KO:K04364]
133347355  SOS1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
133351533  GTPase HRas [KO:K02833]
133361707  GTPase KRas-like [KO:K07827]
133361975  GTPase KRas-like isoform X1 [KO:K07827]
133362052  GTPase KRas-like [KO:K07827]
133362555  GTPase HRas-like [KO:K07827]
133362592  GTPase HRas-like [KO:K07827]
133362703  GTPase KRas-like isoform X1 [KO:K07827]
133362828  GTPase KRas-like [KO:K07827]
133356712  serine/threonine-protein kinase B-raf-like [KO:K04365] [EC:2.7.11.1]
133356826  serine/threonine-protein kinase B-raf-like isoform X1 [KO:K04365] [EC:2.7.11.1]
133351739  serine/threonine-protein kinase B-raf-like isoform X1 [KO:K04365] [EC:2.7.11.1]
133355433  serine/threonine-protein kinase A-Raf-like [KO:K04365] [EC:2.7.11.1]
133356416  LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf-like [KO:K04365] [EC:2.7.11.1]
133355212  dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
133346627  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04369] [EC:2.7.12.2]
133348473  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
133350252  MAP kinase-interacting serine/threonine-protein kinase 1-like isoform X1 [KO:K04372] [EC:2.7.11.1]
133344157  MAP kinase-interacting serine/threonine-protein kinase 1-like [KO:K04372] [EC:2.7.11.1]
133355444  ETS domain-containing protein Elk-1-like [KO:K04375]
133349402  suppressor of cytokine signaling 2-like [KO:K04695]
133345804  suppressor of cytokine signaling 3-like [KO:K04696]
133345854  suppressor of cytokine signaling 3-like [KO:K04696]
133340637  suppressor of cytokine signaling 3-like [KO:K04696]
133348008  suppressor of cytokine signaling 1-like [KO:K04696]
133357920  tyrosine-protein phosphatase non-receptor type 1-like isoform X1 [KO:K05696] [EC:3.1.3.48]
133363007  tyrosine-protein phosphatase non-receptor type 1-like [KO:K05696] [EC:3.1.3.48]
133355899  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K05696] [EC:3.1.3.48]
133350571  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
133354536  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
133341906  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
133357232  phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2-like [KO:K15909] [EC:3.1.3.86]
133357233  LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2-like [KO:K15909] [EC:3.1.3.86]
133345474  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
lrj00010  Glycolysis / Gluconeogenesis
lrj00061  Fatty acid biosynthesis
lrj00500  Starch and sucrose metabolism
lrj04010  MAPK signaling pathway
lrj04070  Phosphatidylinositol signaling system
lrj04210  Apoptosis
KO pathway
ko04910   
LinkDB

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