KEGG   PATHWAY: nmel04012
Entry
nmel04012                   Pathway                                
Name
ErbB signaling pathway - Numida meleagris (helmeted guineafowl)
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
nmel04012  ErbB signaling pathway
nmel04012

Organism
Numida meleagris (helmeted guineafowl) [GN:nmel]
Gene
110399042  EGF; pro-epidermal growth factor [KO:K04357]
110387213  TGFA; protransforming growth factor alpha [KO:K08774]
110398732  AREG; amphiregulin [KO:K09782]
110393050  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110388649  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
110408143  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
110393955  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like isoform X1 [KO:K01116] [EC:3.1.4.11]
110404260  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
110387161  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
110397346  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
110405364  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
110399309  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
110407228  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
110405777  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110387634  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
110400575  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
110388528  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
110408003  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
110393818  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
110406265  CRKL; crk-like protein [KO:K04438]
110407619  CRK; adapter molecule crk isoform X1 [KO:K04438]
110406778  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
110402506  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
110406945  NCK2; cytoplasmic protein NCK2 [KO:K19862]
110391291  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
110397348  PAK2; serine/threonine-protein kinase PAK 2 isoform X1 [KO:K04410] [EC:2.7.11.1]
110403309  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
110389111  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
110395539  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
110401184  serine/threonine-protein kinase PAK 6-like [KO:K05735] [EC:2.7.11.1]
110407172  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110390478  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
110398630  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110405490  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110399325  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110402812  JUN; transcription factor AP-1 [KO:K04448]
110397686  BTC; probetacellulin [KO:K09783]
110405127  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
110398625  EREG; proepiregulin [KO:K09784]
110389140  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
110389501  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
110405232  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
110399647  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
110391258  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
110389019  SHC2; SHC-transforming protein 2 [KO:K17447]
110390178  SHC3; SHC-transforming protein 3 [KO:K17448]
110403695  SHC4; SHC-transforming protein 4 [KO:K17449]
110407421  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
110401960  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110397177  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110400761  HRAS; GTPase HRas [KO:K02833]
110396332  KRAS; GTPase KRas isoform X1 [KO:K07827]
110388133  NRAS; GTPase NRas [KO:K07828]
110394457  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
110404723  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110404031  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110388854  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110406180  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110394505  MYC; myc proto-oncogene protein [KO:K04377]
110397604  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
110399930  NRG3; pro-neuregulin-3, membrane-bound isoform [KO:K05457]
110403554  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
110398160  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110397252  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110408755  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
110389564  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110388756  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110402756  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110396620  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110400745  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110408585  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110407933  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
110387062  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 isoform X1 [KO:K07205]
110399222  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
110390809  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
110388091  CDKN1A; cyclin-dependent kinase inhibitor 1 [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
nmel04010  MAPK signaling pathway
nmel04020  Calcium signaling pathway
nmel04110  Cell cycle
nmel04150  mTOR signaling pathway
KO pathway
ko04012   
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