KEGG   PATHWAY: nwh04910
Entry
nwh04910                    Pathway                                
Name
Insulin signaling pathway - Nematolebias whitei (Rio pearlfish)
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
nwh04910  Insulin signaling pathway
nwh04910

Organism
Nematolebias whitei (Rio pearlfish) [GN:nwh]
Gene
119409113  insb; preproinsulin b [KO:K04526]
119419923  insulin [KO:K04526]
119420379  ins; insulin [KO:K04526]
119415203  insra; insulin receptor a [KO:K04527] [EC:2.7.10.1]
119430640  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
119409467  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
119420295  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
119408688  insulin receptor substrate 2-B [KO:K07187]
119419666  irs2b; insulin receptor substrate 2 [KO:K07187]
119428803  insulin receptor substrate 2 isoform X1 [KO:K07187]
119407692  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119413776  phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
119424477  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119414965  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119415016  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
119430464  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
119411526  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
119417035  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119407666  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119414520  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119425611  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119423421  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
119422614  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119418640  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119427445  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119410556  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119419662  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119422208  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
119428589  gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
119421853  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
119408360  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
119427307  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
119418592  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
119423989  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
119414132  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
119411756  ppp1r3db; protein phosphatase 1, regulatory subunit 3Db [KO:K07189]
119417049  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
119422538  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
119413305  ppp1r3ca; protein phosphatase 1, regulatory subunit 3Ca [KO:K07189]
119413620  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
119423889  protein phosphatase 1 regulatory subunit 3C-like [KO:K07189]
119428057  ppp1r3aa; uncharacterized protein ppp1r3aa [KO:K07189]
119425177  ppp1r3b; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189]
119429896  protein phosphatase 1 regulatory subunit 3E [KO:K07189]
119423417  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
119410594  phkg1a; phosphorylase kinase, gamma 1a (muscle) [KO:K00871] [EC:2.7.11.19]
119422858  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
119426570  phkb; phosphorylase b kinase regulatory subunit beta [KO:K07190]
119408669  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
119426841  calmodulin-like protein 4 [KO:K02183]
119427283  calmodulin-1 [KO:K02183]
119418447  calm1b; calmodulin-1b [KO:K02183]
119410622  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
119408060  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
119427040  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
119420589  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
119420901  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
119425196  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
119421717  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a [KO:K04345] [EC:2.7.11.11]
119407776  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
119422780  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119415051  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
119415820  cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739]
119420988  cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739]
119417704  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
119423926  prkar1ab; protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) b [KO:K04739]
119409953  lipeb; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
119425963  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
119417777  prkcz; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
119415200  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
119409395  LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
119409342  flot1b; flotillin-1b [KO:K07192]
119410979  flotillin-2 [KO:K07192]
119420615  flotillin-2a isoform X1 [KO:K07192]
119425843  flot1a; flotillin-1a [KO:K07192]
119411270  SH2B adapter protein 2 [KO:K07193]
119410877  sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
119411219  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
119420818  E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
119424345  crkl; crk-like protein [KO:K04438]
119419891  adapter molecule crk-like [KO:K04438]
119411077  adapter molecule crk [KO:K04438]
119413739  rap guanine nucleotide exchange factor 1-like [KO:K06277]
119424703  rapgef1b; rap guanine nucleotide exchange factor 1b [KO:K06277]
119410704  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
119423866  exoc7; exocyst complex component 7 isoform X1 [KO:K07195]
119421748  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
119422437  cdc42-interacting protein 4 homolog [KO:K07196]
119421595  srebf1; sterol regulatory element-binding protein 1 [KO:K07197]
119420641  acaca; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119413964  acacb; acetyl-CoA carboxylase [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
119424080  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
119422610  hexokinase-1 [KO:K00844] [EC:2.7.1.1]
119423193  hexokinase-1 [KO:K00844] [EC:2.7.1.1]
119414075  hexokinase-2 [KO:K00844] [EC:2.7.1.1]
119420390  hexokinase-2-like [KO:K00844] [EC:2.7.1.1]
119425956  LOW QUALITY PROTEIN: hexokinase HKDC1-like [KO:K00844] [EC:2.7.1.1]
119413856  gck; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
119430746  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
119407484  5'-AMP-activated protein kinase catalytic subunit alpha-2-like [KO:K07198] [EC:2.7.11.31]
119424490  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
119414094  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
119414596  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
119424914  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
119426468  5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
119412557  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
119418910  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b isoform X1 [KO:K07200]
119415073  5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
119420149  forkhead box protein O1-B-like [KO:K07201]
119410967  foxo1a; forkhead box protein O1-A [KO:K07201]
119409068  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
119423796  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
119419131  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
119424092  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
119424093  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
119413124  fbp2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
119413125  fbp1a; fructose-1,6-bisphosphatase 1a [KO:K03841] [EC:3.1.3.11]
119424748  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
119426665  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
119412717  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
119417726  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
119422283  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
119422732  ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
119420216  rps6kb1a; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
119411127  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
119408076  rps6; 40S ribosomal protein S6 [KO:K02991]
119424793  eukaryotic translation initiation factor 4E-binding protein 2 [KO:K07205]
119408344  eukaryotic translation initiation factor 4E-1A [KO:K03259]
119418451  eif4e1c; eukaryotic translation initiation factor 4E family member 1c [KO:K03259]
119427603  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
119414590  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
119413737  tsc1a; TSC complex subunit 1a [KO:K07206]
119424924  tsc1b; TSC complex subunit 1b [KO:K07206]
119422323  tsc2; tuberin [KO:K07207]
119412556  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
119414746  rheb; GTP-binding protein Rheb [KO:K07208]
119416821  badb; BCL2 associated agonist of cell death b [KO:K02158]
119409401  shc1; SHC-transforming protein 1 [KO:K06279]
119407858  shc2; SHC-transforming protein 2 [KO:K17447]
119424705  shc3; SHC-transforming protein 3 [KO:K17448]
119421558  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
119422314  son of sevenless homolog 1 isoform X1 [KO:K03099]
119427032  sos2; son of sevenless homolog 2 [KO:K03099]
119416207  GTPase HRas [KO:K02833]
119416248  kras; GTPase KRas isoform X1 [KO:K07827]
119421583  zgc:55558 [KO:K07827]
119412941  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
119428176  braf; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
119417510  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
119416306  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119407953  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
119421578  mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
119413751  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119407913  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
119430554  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
119417797  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
119422160  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
119422891  suppressor of cytokine signaling 1-like [KO:K04694]
119428421  socs2; suppressor of cytokine signaling 2 [KO:K04695]
119421001  socs3a; suppressor of cytokine signaling 3a [KO:K04696]
119423749  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
119430261  socs4; suppressor of cytokine signaling 4 [KO:K04697]
119417488  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
119415214  receptor-type tyrosine-protein phosphatase F [KO:K05695] [EC:3.1.3.48]
119412019  mapk8a; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
119408491  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
119424857  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
119413028  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
119408899  inppl1b; inositol polyphosphate phosphatase-like 1b [KO:K15909] [EC:3.1.3.86]
119411108  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
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
nwh00010  Glycolysis / Gluconeogenesis
nwh00061  Fatty acid biosynthesis
nwh00500  Starch and sucrose metabolism
nwh04010  MAPK signaling pathway
nwh04070  Phosphatidylinositol signaling system
nwh04210  Apoptosis
KO pathway
ko04910   
LinkDB

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