KEGG   PATHWAY: gat04012
Entry
gat04012                    Pathway                                
Name
ErbB signaling pathway - Gasterosteus aculeatus (three-spined stickleback)
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
gat04012  ErbB signaling pathway
gat04012

Organism
Gasterosteus aculeatus (three-spined stickleback) [GN:gat]
Gene
120818259  egf; pro-epidermal growth factor isoform X1 [KO:K04357]
120834900  tgfa; protransforming growth factor alpha isoform X1 [KO:K08774]
120816150  egfra; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
120811612  melanoma receptor tyrosine-protein kinase-like isoform X1 [KO:K04361] [EC:2.7.10.1]
120819148  erbb2; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
120823912  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
120808617  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
120825607  calcium/calmodulin-dependent protein kinase type II delta 2 chain-like isoform X1 [KO:K04515] [EC:2.7.11.17]
120819535  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
120820869  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120821702  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
120822206  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
120825380  prkcaa; LOW QUALITY PROTEIN: protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
120828293  prkcab; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
120825887  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
120828414  LOW QUALITY PROTEIN: protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
120809973  prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
120822930  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
120815782  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
120821431  cblb; E3 ubiquitin-protein ligase CBL-B-B isoform X1 [KO:K22517] [EC:2.3.2.27]
120819248  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224]
120828238  stat5a; LOW QUALITY PROTEIN: signal transducer and activator of transcription 5A [KO:K11224]
120835124  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
120828725  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
120810078  focal adhesion kinase 1-like isoform X1 [KO:K05725] [EC:2.7.10.2]
120826323  ptk2aa; LOW QUALITY PROTEIN: protein tyrosine kinase 2aa [KO:K05725] [EC:2.7.10.2]
120831943  crkl; crk-like protein [KO:K04438]
120826481  crk; adapter molecule crk [KO:K04438]
120821629  adapter molecule crk-like [KO:K04438]
120831583  abl1; LOW QUALITY PROTEIN: tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
120823792  abl2; LOW QUALITY PROTEIN: tyrosine-protein kinase ABL2 [KO:K08887] [EC:2.7.10.2]
120811324  nck1b; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
120834224  nck2a; cytoplasmic protein NCK2a [KO:K19862]
120824101  pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
120832922  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:2.7.11.1]
120814884  pak2b; serine/threonine-protein kinase PAK 2b [KO:K04410] [EC:2.7.11.1]
120822004  serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
120822308  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
120807789  pak5; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
120832529  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
120814746  serine/threonine-protein kinase PAK 6-like [KO:K05735] [EC:2.7.11.1]
120827864  map2k4a; dual specificity mitogen-activated protein kinase kinase 4a isoform X1 [KO:K04430] [EC:2.7.12.2]
120825459  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
120831463  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120817444  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
120819217  mapk8b; LOW QUALITY PROTEIN: mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
120820300  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120831506  june; junE proto-oncogene, AP-1 transcription factor subunit isoform X1 [KO:K04448]
120824340  jun; transcription factor AP-1 [KO:K04448]
120815715  transcription factor AP-1-like [KO:K04448]
120815086  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
120831637  btc; probetacellulin isoform X1 [KO:K09783]
120817552  hbegfa; heparin-binding EGF-like growth factor a [KO:K08523]
120830311  proepiregulin-like isoform X1 [KO:K09784]
120835587  erbb3a; receptor tyrosine-protein kinase erbB-3a isoform X1 [KO:K05084] [EC:2.7.10.1]
120829080  erbb3b; receptor tyrosine-protein kinase erbB-3b isoform X1 [KO:K05084] [EC:2.7.10.1]
120818449  nrg2b; neuregulin 2b isoform X1 [KO:K05456]
120821391  nrg2a; neuregulin 2a isoform X1 [KO:K05456]
120833897  receptor tyrosine-protein kinase erbB-4-like isoform X1 [KO:K05085] [EC:2.7.10.1]
120825010  si:ch73-383l1.1; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
120810662  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
120823634  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
120831599  shc3; SHC-transforming protein 3 [KO:K17448]
120832530  SHC-transforming protein 1-like isoform X1 [KO:K17449]
120827679  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
120832739  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
120824577  son of sevenless homolog 1-like [KO:K03099]
120808880  GTPase HRas [KO:K02833]
120812270  GTPase HRas-like [KO:K02833]
120808991  GTPase KRas isoform X1 [KO:K07827]
120827241  zgc:55558 [KO:K07827]
120812377  kras; GTPase KRas isoform X1 [KO:K07827]
120830450  araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
120817257  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
120829430  raf1a; LOW QUALITY PROTEIN: raf-1 proto-oncogene, serine/threonine kinase a [KO:K04366] [EC:2.7.11.1]
120808861  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120816299  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
120823910  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
120831071  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120827198  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120811943  myca; LOW QUALITY PROTEIN: transcriptional regulator Myc-A [KO:K04377]
120834660  mych; myelocytomatosis oncogene homolog [KO:K04377]
120825037  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
120821470  GRB2-associated-binding protein 1-like isoform X1 [KO:K09593]
120819435  nrg3b; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
120820640  pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
120809030  pro-neuregulin-4, membrane-bound isoform-like [KO:K05458]
120812882  pro-neuregulin-4, membrane-bound isoform-like [KO:K05458]
120815991  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120823571  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
120829803  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120820925  pik3cb; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
120822125  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120831616  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
120816124  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
120823475  phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649]
120823622  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
120830750  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
120815842  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120832554  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120816700  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120825835  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120820483  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120821432  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
120829137  mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
120825409  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
120821610  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
120828045  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
120831516  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
120821354  badb; BCL2 associated agonist of cell death b [KO:K02158]
120833868  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120809056  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
120812631  cyclin-dependent kinase inhibitor 1B-like isoform X1 [KO:K06624]
120834939  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
120817084  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Reference
  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
  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
gat04010  MAPK signaling pathway
gat04020  Calcium signaling pathway
gat04110  Cell cycle
gat04150  mTOR signaling pathway
KO pathway
ko04012   
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