KEGG   PATHWAY: amex04012
Entry
amex04012                   Pathway                                
Name
ErbB signaling pathway - Astyanax mexicanus (Mexican tetra)
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
amex04012  ErbB signaling pathway
amex04012

Organism
Astyanax mexicanus (Mexican tetra) [GN:amex]
Gene
103045727  egf; pro-epidermal growth factor [KO:K04357]
103044858  protransforming growth factor alpha-like [KO:K08774]
103032492  epidermal growth factor receptor-like isoform X1 [KO:K04361] [EC:2.7.10.1]
103031629  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
103042851  erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
103023099  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
103036277  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
103043420  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103033831  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
103030568  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
103044561  camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X11 [KO:K04515] [EC:2.7.11.17]
103032713  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
103041877  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
103045689  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
103044047  protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
111192909  LOW QUALITY PROTEIN: protein kinase C alpha type-like [KO:K02677] [EC:2.7.11.13]
103036012  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103025973  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103032411  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
103034711  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
103033010  signal transducer and activator of transcription 5B [KO:K11224]
103042656  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224]
103038924  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
107197607  proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:2.7.10.2]
103042998  proto-oncogene tyrosine-protein kinase Src-like isoform X5 [KO:K05704] [EC:2.7.10.2]
103041623  ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
103033402  focal adhesion kinase 1 isoform X5 [KO:K05725] [EC:2.7.10.2]
103044277  crkl; crk-like protein [KO:K04438]
103038949  adapter molecule crk-like [KO:K04438]
103035530  crk; adapter molecule crk [KO:K04438]
103046185  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
103022317  abl2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
103027024  nck1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
103038818  cytoplasmic protein NCK2 [KO:K19862]
103023033  nck2; cytoplasmic protein NCK2 [KO:K19862]
103037975  pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
103022965  pak2; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
103038595  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:2.7.11.1]
103043289  serine/threonine-protein kinase PAK 3-like isoform X1 [KO:K05733] [EC:2.7.11.1]
103028438  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
103023523  pak5; serine/threonine-protein kinase PAK 5 isoform X2 [KO:K05736] [EC:2.7.11.1]
103035957  pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
103030407  serine/threonine-protein kinase PAK 6-like isoform X1 [KO:K05735] [EC:2.7.11.1]
103045018  map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
103042940  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
103024363  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
103043065  LOW QUALITY PROTEIN: mitogen-activated protein kinase 10-like [KO:K04440] [EC:2.7.11.24]
103040580  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103035319  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103034138  mitogen-activated protein kinase 8A isoform X1 [KO:K04440] [EC:2.7.11.24]
103021920  transcription factor AP-1-like [KO:K04448]
103026868  jun; transcription factor AP-1 [KO:K04448]
103034577  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
111191478  probetacellulin-like [KO:K09783]
103025626  proheparin-binding EGF-like growth factor [KO:K08523]
103027828  proheparin-binding EGF-like growth factor [KO:K08523]
103028053  erbb3; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
103032103  receptor tyrosine-protein kinase erbB-3-like isoform X1 [KO:K05084] [EC:2.7.10.1]
103034938  nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
103042778  pro-neuregulin-2, membrane-bound isoform-like isoform X1 [KO:K05456]
103028723  nrg2; LOW QUALITY PROTEIN: pro-neuregulin-2, membrane-bound isoform [KO:K05456]
103033543  erbb4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
103038099  receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
103030808  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
103026451  LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
103034159  LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
111188768  growth factor receptor-bound protein 2-like [KO:K04364]
111191028  growth factor receptor-bound protein 2 [KO:K04364]
103046713  growth factor receptor-bound protein 2 [KO:K04364]
103037386  sos2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
103028577  sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103021516  hras; GTPase HRas [KO:K02833]
103040103  GTPase HRas [KO:K02833]
103038241  GTPase KRas isoform X1 [KO:K07827]
103023536  GTPase HRas-like [KO:K07827]
103039914  nras; GTPase NRas [KO:K07828]
103043654  araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
103036930  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
103027930  RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103025658  RAF proto-oncogene serine/threonine-protein kinase-like isoform X1 [KO:K04366] [EC:2.7.11.1]
103028644  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103030512  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103041389  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103047585  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103038167  transcriptional regulator Myc-B-like [KO:K04377]
103033997  transcriptional regulator Myc [KO:K04377]
103043031  gab1; GRB2-associated-binding protein 1 isoform X4 [KO:K09593]
103044368  pro-neuregulin-3, membrane-bound isoform-like isoform X1 [KO:K05457]
103042844  nrg3; pro-neuregulin-3, membrane-bound isoform [KO:K05457]
103022447  nrg4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
103032909  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103045036  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103041606  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103022173  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111190801  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
103035767  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
103029972  pik3r3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103046618  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103040659  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103026930  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103023390  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103040186  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
103024575  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103042377  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
103035647  rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
103031203  rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
103026948  eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
103032659  bcl2-associated agonist of cell death-like isoform X1 [KO:K02158]
103047163  uncharacterized protein LOC103047163 [KO:K02158]
103021870  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103043574  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
103030485  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
103025923  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
103047217  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103041774  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
  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
amex04010  MAPK signaling pathway
amex04020  Calcium signaling pathway
amex04110  Cell cycle
amex04150  mTOR signaling pathway
KO pathway
ko04012   
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