KEGG   PATHWAY: esp04012
Entry
esp04012                    Pathway                                
Name
ErbB signaling pathway - Etheostoma spectabile (orangethroat darter)
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
esp04012  ErbB signaling pathway
esp04012

Organism
Etheostoma spectabile (orangethroat darter) [GN:esp]
Gene
116696510  egf; pro-epidermal growth factor [KO:K04357]
116688024  protransforming growth factor alpha-like [KO:K08774]
116698815  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116671269  erbb2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
116692557  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
116695236  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like isoform X1 [KO:K01116] [EC:3.1.4.11]
116693373  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2-like isoform X1 [KO:K05859] [EC:3.1.4.11]
116693374  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2-like isoform X1 [KO:K05859] [EC:3.1.4.11]
116705273  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116686178  calcium/calmodulin-dependent protein kinase type II subunit beta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116669783  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
116686615  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
116671728  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116688857  calcium/calmodulin-dependent protein kinase type II subunit beta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116670566  prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116702478  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
116705456  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116703070  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116691362  protein kinase C alpha type-like isoform X1 [KO:K19663] [EC:2.7.11.13]
116700199  E3 ubiquitin-protein ligase CBL-like isoform X1 [KO:K04707] [EC:2.3.2.27]
116687126  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
116700422  cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
116704597  signal transducer and activator of transcription 5B-like [KO:K11224]
116702316  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224]
116671513  signal transducer and activator of transcription 5B-like [KO:K11224]
116692732  LOW QUALITY PROTEIN: proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:2.7.10.2]
116687594  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
116691433  LOW QUALITY PROTEIN: focal adhesion kinase 1-like [KO:K05725] [EC:2.7.10.2]
116701641  focal adhesion kinase 1-like isoform X1 [KO:K05725] [EC:2.7.10.2]
116674771  crk; adapter molecule crk [KO:K04438]
116700737  adapter molecule crk-like [KO:K04438]
116703898  crkl; crk-like protein [KO:K04438]
116704534  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
116695807  abl2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
116672014  nck1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
116697767  nck2; cytoplasmic protein NCK2 [KO:K19862]
116685041  serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
116670013  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:2.7.11.1]
116695614  pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
116700229  serine/threonine-protein kinase PAK 3-like isoform X1 [KO:K05733] [EC:2.7.11.1]
116686972  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
116706251  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
116670002  pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
116705506  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04430] [EC:2.7.12.2]
116671100  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
116703458  map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
116705548  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116697416  mitogen-activated protein kinase 9-like [KO:K04440] [EC:2.7.11.24]
116705432  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116671539  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116703876  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116677748  transcription factor AP-1-like [KO:K04448]
116698745  transcription factor AP-1-like [KO:K04448]
116695201  transcription factor AP-1-like [KO:K04448]
116704060  transcription factor AP-1-like [KO:K04448]
116679543  ETS domain-containing protein Elk-1-like [KO:K04375]
116704810  probetacellulin-like isoform X1 [KO:K09783]
116696593  proheparin-binding EGF-like growth factor [KO:K08523]
116688848  ereg; proepiregulin isoform X1 [KO:K09784]
116692233  receptor tyrosine-protein kinase erbB-3-like [KO:K05084] [EC:2.7.10.1]
116688361  erbb3; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
116685920  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
116700958  nrg2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
116673917  erbb4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
116698166  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
116691703  shc1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
116696202  LOW QUALITY PROTEIN: SHC-transforming protein 2-like [KO:K17447]
116704435  shc3; SHC-transforming protein 3 [KO:K17448]
116703619  shc4; SHC-transforming protein 4 isoform X1 [KO:K17449]
116702397  grb2; growth factor receptor-bound protein 2 [KO:K04364]
116678819  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
116669702  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116694245  hras; GTPase HRas [KO:K02833]
116694484  kras; GTPase KRas isoform X1 [KO:K07827]
116703772  GTPase HRas-like [KO:K07827]
116689928  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
116673193  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
116693071  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116694773  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116699426  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
116699428  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
116695172  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116690322  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116703753  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
116672376  myc; myc proto-oncogene protein isoform X1 [KO:K04377]
116706143  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
116669527  LOW QUALITY PROTEIN: GRB2-associated-binding protein 1-like [KO:K09593]
116705073  pro-neuregulin-3, membrane-bound isoform-like isoform X1 [KO:K05457]
116671090  pro-neuregulin-3, membrane-bound isoform-like isoform X1 [KO:K05457]
116694079  nrg4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
116675754  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
116678381  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
116699195  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
116692529  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116695417  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
116698567  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
116699207  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
116695430  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116696146  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
116689915  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
116704085  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116673342  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116705099  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116670120  akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116673142  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
116692591  mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
116673415  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
116700771  ribosomal protein S6 kinase beta-1-like isoform X1 [KO:K04688] [EC:2.7.11.1]
116694798  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
116689334  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
116703982  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
116707131  bad; bcl2-associated agonist of cell death [KO:K02158]
116698290  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116693641  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
116672831  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
116687706  cyclin-dependent kinase inhibitor 1-like isoform X1 [KO:K06625]
116673033  cyclin-dependent kinase inhibitor 1-like [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
esp04010  MAPK signaling pathway
esp04020  Calcium signaling pathway
esp04110  Cell cycle
esp04150  mTOR signaling pathway
KO pathway
ko04012   
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