KEGG   PATHWAY: eee04012
Entry
eee04012                    Pathway                                
Name
ErbB signaling pathway - Electrophorus electricus (electric eel)
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
eee04012  ErbB signaling pathway
eee04012

Organism
Electrophorus electricus (electric eel) [GN:eee]
Gene
113579942  egf; pro-epidermal growth factor isoform X1 [KO:K04357]
113575949  protransforming growth factor alpha-like [KO:K08774]
113587946  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
113590490  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
113576854  erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
113588884  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
113577174  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
113577666  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
113571482  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
113587336  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
113587439  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
113572944  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
113579297  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
113583472  camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
113575317  protein kinase C alpha type-like isoform X1 [KO:K02677] [EC:2.7.11.13]
113590761  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
113588773  protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
113580901  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
113579444  cbl; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
113571604  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
113581977  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224]
113591522  signal transducer and activator of transcription 5B-like [KO:K11224]
113576303  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
113572439  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
113571245  focal adhesion kinase 1-like [KO:K05725] [EC:2.7.10.2]
113590645  ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
113582116  adapter molecule crk-like [KO:K04438]
113569771  adapter molecule crk-like [KO:K04438]
113570756  crkl; crk-like protein [KO:K04438]
113583945  LOW QUALITY PROTEIN: tyrosine-protein kinase ABL1-like [KO:K06619] [EC:2.7.10.2]
113572036  LOW QUALITY PROTEIN: tyrosine-protein kinase ABL2-like [KO:K08887] [EC:2.7.10.2]
113584767  LOW QUALITY PROTEIN: cytoplasmic protein NCK1-like [KO:K07365]
113584888  cytoplasmic protein NCK2-like [KO:K19862]
113574073  cytoplasmic protein NCK2-like [KO:K19862]
113576959  pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
113576367  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:2.7.11.1]
113579372  serine/threonine-protein kinase PAK 2-like isoform X1 [KO:K04410] [EC:2.7.11.1]
113586857  serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
113569760  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
113589839  serine/threonine-protein kinase PAK 5-like isoform X1 [KO:K05736] [EC:2.7.11.1]
113571327  pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
113591405  dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
113570943  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
113580330  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
113578033  mitogen-activated protein kinase 8B isoform X1 [KO:K04440] [EC:2.7.11.24]
113574265  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
113586292  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
113586306  mitogen-activated protein kinase 10-like [KO:K04440] [EC:2.7.11.24]
113571260  mitogen-activated protein kinase 9-like [KO:K04440] [EC:2.7.11.24]
113589106  transcription factor AP-1-like [KO:K04448]
113582834  transcription factor AP-1-like [KO:K04448]
113568701  transcription factor AP-1-like [KO:K04448]
113585820  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
113570753  probetacellulin-like isoform X1 [KO:K09783]
113585265  proheparin-binding EGF-like growth factor [KO:K08523]
113581493  proheparin-binding EGF-like growth factor [KO:K08523]
113581542  erbb3; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
113581376  receptor tyrosine-protein kinase erbB-3-like isoform X1 [KO:K05084] [EC:2.7.10.1]
113570043  nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
113573372  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
113585259  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
113579187  erbb4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
113579192  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
113590613  shc1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
113587209  shc2; SHC-transforming protein 2 [KO:K17447]
113573720  SHC-transforming protein 3-like [KO:K17448]
113575233  growth factor receptor-bound protein 2 [KO:K04364]
113584789  growth factor receptor-bound protein 2-like [KO:K04364]
113577720  son of sevenless homolog 2-like isoform X1 [KO:K03099]
113578009  sos1; son of sevenless homolog 1 [KO:K03099]
113579694  GTPase HRas [KO:K02833]
113581312  hras; GTPase HRas [KO:K02833]
113588524  GTPase KRas isoform X1 [KO:K07827]
113589852  GTPase HRas-like [KO:K07827]
113577375  nras; GTPase NRas [KO:K07828]
113588109  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
113572532  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
113580611  RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
113572287  RAF proto-oncogene serine/threonine-protein kinase-like isoform X1 [KO:K04366] [EC:2.7.11.1]
113588584  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
113588939  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
113584672  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
113585589  mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
113592047  mitogen-activated protein kinase 1-like isoform X1 [KO:K04371] [EC:2.7.11.24]
113589820  LOW QUALITY PROTEIN: transcriptional regulator Myc-B-like [KO:K04377]
113573843  transcriptional regulator Myc-2-like [KO:K04377]
113589975  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
113587874  pro-neuregulin-3, membrane-bound isoform-like [KO:K05457]
113583982  pro-neuregulin-3, membrane-bound isoform-like [KO:K05457]
113581761  nrg4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
113568728  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113584997  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113581289  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
113567981  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113587165  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
113588232  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113571342  akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113578378  akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113568414  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
113579639  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
113584326  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
113584368  rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
113568160  ribosomal protein S6 kinase beta-2-like isoform X1 [KO:K04688] [EC:2.7.11.1]
113579817  bcl2-associated agonist of cell death-like isoform X1 [KO:K02158]
113586001  bcl2-associated agonist of cell death-like [KO:K02158]
113578561  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
113572522  cyclin-dependent kinase inhibitor 1B-like isoform X1 [KO:K06624]
113583571  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
113586971  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
113573558  cyclin-dependent kinase inhibitor 1-like isoform X1 [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
eee04010  MAPK signaling pathway
eee04020  Calcium signaling pathway
eee04110  Cell cycle
eee04150  mTOR signaling pathway
KO pathway
ko04012   
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