KEGG   PATHWAY: sscv04910
Entry
sscv04910                   Pathway                                
Name
Insulin signaling pathway - Syngnathus scovelli (Gulf pipefish)
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
sscv04910  Insulin signaling pathway
sscv04910

Organism
Syngnathus scovelli (Gulf pipefish) [GN:sscv]
Gene
125965738  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
125965791  prkab1b; 5'-AMP-activated protein kinase subunit beta-1b [KO:K07199]
125965877  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
125966671  phkb; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
125966946  [KO:K00844] [EC:2.7.1.1]
125967139  phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
125967174  [KO:K07189]
125967251  socs4; suppressor of cytokine signaling 4 [KO:K04697]
125967267  calml4a; calmodulin-like protein 4a [KO:K02183]
125967558  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
125967574  [KO:K17449]
125968433  rps6; small ribosomal subunit protein eS6 [KO:K02991]
125968487  [KO:K03099]
125968716  [KO:K07196]
125968739  rptor; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
125968895  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
125968917  akt3b; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125968949  mknk2b; MAP kinase-interacting serine/threonine-protein kinase 2b [KO:K04372] [EC:2.7.11.1]
125969150  [KO:K00844] [EC:2.7.1.1]
125969457  [KO:K04688] [EC:2.7.11.1]
125969583  tsc2; tuberin isoform X1 [KO:K07207]
125969625  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
125970052  kras; GTPase KRas isoform X1 [KO:K07827]
125970651  [KO:K02833]
125971154  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
125971263  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
125971747  mknk1; MAP kinase-interacting serine/threonine-protein kinase 1 [KO:K04372] [EC:2.7.11.1]
125971952  crk; adapter molecule crk [KO:K04438]
125972100  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
125972106  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
125972116  [KO:K00871] [EC:2.7.11.19]
125972428  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
125972506  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125972530  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125972586  foxo1a; forkhead box protein O1-A [KO:K07201]
125972694  [KO:K07193]
125972712  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
125972754  inppl1a; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A [KO:K15909] [EC:3.1.3.86]
125973398  insrb; insulin receptor b [KO:K04527] [EC:2.7.10.1]
125973453  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125973487  irs2b; insulin receptor substrate 2 [KO:K07187]
125973987  ptprfa; protein tyrosine phosphatase receptor type Fa isoform X1 [KO:K05695] [EC:3.1.3.48]
125974162  prkag3b; 5'-AMP-activated protein kinase subunit gamma-3b isoform X1 [KO:K07200]
125974749  flot1b; flotillin-1b isoform X1 [KO:K07192]
125975384  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
125975658  lipeb; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
125976195  [KO:K02649]
125976273  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125976682  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
125976744  ppp1r3db; protein phosphatase 1, regulatory subunit 3Db [KO:K07189]
125977257  prkar2ab; protein kinase, cAMP-dependent, regulatory, type II, alpha, B [KO:K04739]
125977719  pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
125977776  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
125978137  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
125978191  [KO:K07189]
125978275  rhoq; rho-related GTP-binding protein RhoQ [KO:K07194]
125978276  [KO:K06086]
125978334  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125978384  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
125978695  eif4e1c; eukaryotic translation initiation factor 4E family member 1c [KO:K03259]
125978941  [KO:K01106] [EC:3.1.3.56]
125979009  akt3a; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125979286  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
125979430  tsc1b; TSC complex subunit 1b isoform X1 [KO:K07206]
125979503  ppp1r3b; protein phosphatase 1 regulatory subunit 3B [KO:K07189]
125979601  shc3; SHC-transforming protein 3 [KO:K17448]
125979652  prkab1a; 5'-AMP-activated protein kinase subunit beta-1a [KO:K07199]
125979754  [KO:K03841] [EC:3.1.3.11]
125979930  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X1 [KO:K06277]
125979979  [KO:K07205]
125980080  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125980183  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125980191  crkl; crk-like protein [KO:K04438]
125980496  eif4eb; eukaryotic translation initiation factor 4eb [KO:K03259]
125980688  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125980949  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
125980977  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
125981064  [KO:K06269] [EC:3.1.3.16]
125981264  [KO:K02183]
125981416  phka1a; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
125981728  [KO:K04526]
125981783  acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125982105  si:ch211-284e13.4; insulin receptor substrate 1-B [KO:K16172]
125982119  [KO:K07201]
125982242  [KO:K04438]
125982330  [KO:K00844] [EC:2.7.1.1]
125982505  [KO:K04707] [EC:2.3.2.27]
125982557  pygma; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
125982588  [KO:K06269] [EC:3.1.3.16]
125982694  [KO:K07192]
125983169  zgc:55558; GTPase KRas [KO:K07827]
125983268  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
125983547  socs1a; suppressor of cytokine signaling 1a [KO:K04694]
125983596  prkar1aa; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739]
125983650  prkar1b; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739]
125983683  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125983731  [KO:K00688] [EC:2.4.1.1]
125983785  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
125983844  trip10a; cdc42-interacting protein 4 homolog isoform X1 [KO:K07196]
125983880  [KO:K04345] [EC:2.7.11.11]
125983913  [KO:K04696]
125984053  [KO:K07187]
125984112  gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
125984173  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
125984242  srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197]
125984489  [KO:K07200]
125984519  insra; insulin receptor a isoform X1 [KO:K04527] [EC:2.7.10.1]
125984531  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
125984586  [KO:K00922] [EC:2.7.1.153]
125984961  prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
125984962  eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259]
125985035  rheb; GTP-binding protein Rheb [KO:K07208]
125985110  [KO:K05695] [EC:3.1.3.48]
125985301  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
125985400  [KO:K02649]
125985535  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125985739  pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
125986033  [KO:K07200]
125986561  flot1a; flotillin-1a [KO:K07192]
125987207  eif4ea; eukaryotic translation initiation factor 4E-1A [KO:K03259]
125987725  ppp1r3da; protein phosphatase 1, regulatory subunit 3Da [KO:K07189]
125987804  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
125987838  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
125987861  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
125988166  prkar2aa; protein kinase, cAMP-dependent, regulatory, type II, alpha A [KO:K04739]
125988346  [KO:K07187]
125988595  prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
125988606  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125988838  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
125989088  ptpn1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
125989260  inppl1b; inositol polyphosphate phosphatase-like 1b isoform X2 [KO:K15909] [EC:3.1.3.86]
125990163  [KO:K02183]
125990927  g6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
125990945  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125991102  pdpk1b; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
125991111  phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
125991305  si:ch73-335l21.1; insulin receptor substrate 1-B [KO:K16172]
125991479  [KO:K04739]
125991538  socs3b; suppressor of cytokine signaling 3b [KO:K04696]
125991556  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
125991592  fasn; fatty acid synthase [KO:K00665] [EC:2.3.1.85]
125991643  exoc7; exocyst complex component 7 isoform X6 [KO:K07195]
125991745  g6pc1a.2; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
125991746  g6pc1a.1; glucose-6-phosphatase a, catalytic subunit, tandem duplicate 1 [KO:K01084] [EC:3.1.3.9]
125991958  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125992038  gys2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
125992377  [KO:K07191]
125992421  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
125993043  [KO:K03259]
125993156  badb; BCL2 associated agonist of cell death b [KO:K02158]
125993585  [KO:K07205]
125993760  acacb; acetyl-CoA carboxylase isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
125993784  [KO:K07206]
125993888  hk2; hexokinase-2 isoform X1 [KO:K00844] [EC:2.7.1.1]
125993934  inpp5l; inositol polyphosphate-5-phosphatase A [KO:K01106] [EC:3.1.3.56]
125994011  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
125994016  [KO:K02649]
125994063  [KO:K04526]
125994079  gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
125994114  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125994141  fbp1a; fructose-1,6-bisphosphatase 1a [KO:K03841] [EC:3.1.3.11]
125994145  fbp2; fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
125994440  ppp1r3c2b; protein phosphatase 1 regulatory subunit 3C-B-like [KO:K07189]
125994756  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
137839748  lipea; lipase, hormone-sensitive a [KO:K07188] [EC:3.1.1.79]
137840355  [KO:K04739]
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
sscv00010  Glycolysis / Gluconeogenesis
sscv00061  Fatty acid biosynthesis
sscv00500  Starch and sucrose metabolism
sscv04010  MAPK signaling pathway
sscv04070  Phosphatidylinositol signaling system
sscv04210  Apoptosis
KO pathway
ko04910   

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