KEGG   PATHWAY: gmu04012
Entry
gmu04012                    Pathway                                
Name
ErbB signaling pathway - Girardinichthys multiradiatus (darkedged splitfin)
Description
The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase.
Class
Environmental Information Processing; Signal transduction
Pathway map
gmu04012  ErbB signaling pathway
gmu04012

Organism
Girardinichthys multiradiatus (darkedged splitfin) [GN:gmu]
Gene
124860567  egf; pro-epidermal growth factor [KO:K04357]
124856394  tgfa; protransforming growth factor alpha [KO:K08774]
124858134  melanoma receptor tyrosine-protein kinase-like isoform X1 [KO:K04361] [EC:2.7.10.1]
124869445  egfra; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
124875242  erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
124869858  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
124873539  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like isoform X1 [KO:K01116] [EC:3.1.4.11]
124860019  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
124876485  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
124877446  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
124858726  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
124872448  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
124881210  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
124867851  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
124875180  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
124862966  protein kinase C alpha type-like isoform X1 [KO:K02677] [EC:2.7.11.13]
124864797  protein kinase C alpha type-like isoform X1 [KO:K02677] [EC:2.7.11.13]
124867838  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
124862727  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
124864744  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
124868119  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
124866124  prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
124876272  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
124883956  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
124862983  signal transducer and activator of transcription 5B-like [KO:K11224]
124864740  signal transducer and activator of transcription 5B-like [KO:K11224]
124874677  signal transducer and activator of transcription 5B-like [KO:K11224]
124870123  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
124856497  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
124866061  focal adhesion kinase 1-like isoform X1 [KO:K05725] [EC:2.7.10.2]
124878855  ptk2aa; protein tyrosine kinase 2aa isoform X1 [KO:K05725] [EC:2.7.10.2]
124876940  adapter molecule crk-like [KO:K04438]
124884098  crk; adapter molecule crk [KO:K04438]
124872914  crkl; crk-like protein isoform X1 [KO:K04438]
124872546  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
124873880  abl2; tyrosine-protein kinase ABL2 [KO:K08887] [EC:2.7.10.2]
124857862  nck1b; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
124871787  nck2a; cytoplasmic protein NCK2a [KO:K19862]
124855774  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:2.7.11.1]
124873465  pak2b; serine/threonine-protein kinase PAK 2b [KO:K04410] [EC:2.7.11.1]
124875948  serine/threonine-protein kinase PAK 3-like isoform X1 [KO:K05733] [EC:2.7.11.1]
124883970  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
124882079  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
124855875  serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05735] [EC:2.7.11.1]
124881990  serine/threonine-protein kinase PAK 4-like isoform X1 [KO:K05735] [EC:2.7.11.1]
124862979  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
124864757  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
124875573  map2k4b; dual specificity mitogen-activated protein kinase kinase 4b isoform X1 [KO:K04430] [EC:2.7.12.2]
124868478  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
124872468  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
124859135  mapk8a; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
124860150  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
124875307  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
124870122  transcription factor Jun-like [KO:K04448]
124873148  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
124873314  jun; transcription factor AP-1 [KO:K04448]
124868529  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
124873156  btc; probetacellulin isoform X1 [KO:K09783]
124859891  hbegfa; heparin-binding EGF-like growth factor a [KO:K08523]
124877462  proepiregulin-like [KO:K09784]
124857405  erbb3a; receptor tyrosine-protein kinase erbB-3a isoform X1 [KO:K05084] [EC:2.7.10.1]
124874066  erbb3b; receptor tyrosine-protein kinase erbB-3b isoform X1 [KO:K05084] [EC:2.7.10.1]
124876275  nrg2a; neuregulin 2a [KO:K05456]
124860586  nrg2b; neuregulin 2b isoform X1 [KO:K05456]
124871474  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
124861969  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
124865598  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
124874121  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
124872742  shc3; SHC-transforming protein 3 [KO:K17448]
124867254  SHC-transforming protein 4-like [KO:K17449]
124863357  growth factor receptor-bound protein 2 [KO:K04364]
124863971  growth factor receptor-bound protein 2 [KO:K04364]
124868143  son of sevenless homolog 1-like isoform X1 [KO:K03099]
124855236  sos2; son of sevenless homolog 2 [KO:K03099]
124882413  GTPase HRas [KO:K02833]
124863530  GTPase KRas-like isoform X1 [KO:K07827]
124864335  GTPase KRas-like isoform X1 [KO:K07827]
124879131  kras; GTPase KRas isoform X1 [KO:K07827]
124878222  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
124883025  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
124866030  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
124856513  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124874089  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
124863274  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
124864295  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
124877799  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124869726  transcriptional regulator Myc-B-like [KO:K04377]
124858439  myca; transcriptional regulator Myc-A isoform X1 [KO:K04377]
124856963  mych; myelocytomatosis oncogene homolog [KO:K04377]
124880203  GRB2-associated-binding protein 1-like [KO:K09593]
124868151  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
124859340  pro-neuregulin-3, membrane-bound isoform-like isoform X1 [KO:K05457]
124875453  nrg3b; pro-neuregulin-3, membrane-bound isoform [KO:K05457]
124883165  pro-neuregulin-4, membrane-bound isoform-like [KO:K05458]
124870477  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124884243  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124873577  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
124880409  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
124875686  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
124870480  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
124877742  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
124872596  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124873683  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
124873763  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
124869460  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124883780  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124858601  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124867765  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124855241  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124867337  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
124876390  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
124884239  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
124868300  ribosomal protein S6 kinase beta-2-like isoform X1 [KO:K04688] [EC:2.7.11.1]
124877350  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
124872717  eukaryotic translation initiation factor 4E-binding protein 1-like isoform X1 [KO:K07205]
124880840  badb; BCL2 associated agonist of cell death b [KO:K02158]
124871205  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
124883195  cdkn1ba; cyclin-dependent kinase inhibitor 1Ba [KO:K06624]
124861208  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
124857035  cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
124882752  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:14967450
  Authors
Marmor MD, Skaria KB, Yarden Y.
  Title
Signal transduction and oncogenesis by ErbB/HER receptors.
  Journal
Int J Radiat Oncol Biol Phys 58:903-13 (2004)
DOI:10.1016/j.ijrobp.2003.06.002
Reference
PMID:11252954
  Authors
Yarden Y, Sliwkowski MX.
  Title
Untangling the ErbB signalling network.
  Journal
Nat Rev Mol Cell Biol 2:127-37 (2001)
DOI:10.1038/35052073
Reference
PMID:16829981
  Authors
Citri A, Yarden Y.
  Title
EGF-ERBB signalling: towards the systems level.
  Journal
Nat Rev Mol Cell Biol 7:505-16 (2006)
DOI:10.1038/nrm1962
Reference
PMID:17000658
  Authors
Scaltriti M, Baselga J.
  Title
The epidermal growth factor receptor pathway: a model for targeted therapy.
  Journal
Clin Cancer Res 12:5268-72 (2006)
DOI:10.1158/1078-0432.CCR-05-1554
Reference
PMID:16377102
  Authors
Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS.
  Title
Epidermal growth factor receptor (EGFR) signaling in cancer.
  Journal
Gene 366:2-16 (2006)
DOI:10.1016/j.gene.2005.10.018
Reference
PMID:14744244
  Authors
Holbro T, Hynes NE.
  Title
ErbB receptors: directing key signaling networks throughout life.
  Journal
Annu Rev Pharmacol Toxicol 44:195-217 (2004)
DOI:10.1146/annurev.pharmtox.44.101802.121440
Reference
PMID:12851486
  Authors
Liang J, Slingerland JM.
  Title
Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.
  Journal
Cell Cycle 2:339-45 (2003)
DOI:10.4161/cc.2.4.433
Reference
PMID:15864276
  Authors
Hynes NE, Lane HA.
  Title
ERBB receptors and cancer: the complexity of targeted inhibitors.
  Journal
Nat Rev Cancer 5:341-54 (2005)
DOI:10.1038/nrc1609
Reference
PMID:16729045
  Authors
Oda K, Matsuoka Y, Funahashi A, Kitano H.
  Title
A comprehensive pathway map of epidermal growth factor receptor signaling.
  Journal
Mol Syst Biol 1:2005.0010 (2005)
DOI:10.1038/msb4100014
Reference
PMID:16729043
  Authors
Schulze WX, Deng L, Mann M.
  Title
Phosphotyrosine interactome of the ErbB-receptor kinase family.
  Journal
Mol Syst Biol 1:2005.0008 (2005)
DOI:10.1038/msb4100012
Reference
PMID:10880430
  Authors
Olayioye MA, Neve RM, Lane HA, Hynes NE.
  Title
The ErbB signaling network: receptor heterodimerization in development and cancer.
  Journal
EMBO J 19:3159-67 (2000)
DOI:10.1093/emboj/19.13.3159
Reference
PMID:9872057
  Authors
McCarty JH.
  Title
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.
  Journal
Bioessays 20:913-21 (1998)
DOI:10.1002/(SICI)1521-1878(199811)20:11<913::AID-BIES6>3.0.CO;2-T
Reference
PMID:15863494
  Authors
Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE.
  Title
ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.
  Journal
J Biol Chem 280:24175-80 (2005)
DOI:10.1074/jbc.M414044200
Reference
PMID:10490623
  Authors
Muthuswamy SK, Gilman M, Brugge JS.
  Title
Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
  Journal
Mol Cell Biol 19:6845-57 (1999)
DOI:10.1128/MCB.19.10.6845
Reference
PMID:9642287
  Authors
Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M.
  Title
Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.
  Journal
J Biol Chem 273:17186-91 (1998)
DOI:10.1074/jbc.273.27.17186
Related
pathway
gmu04010  MAPK signaling pathway
gmu04020  Calcium signaling pathway
gmu04110  Cell cycle
gmu04150  mTOR signaling pathway
KO pathway
ko04012   
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