KEGG   PATHWAY: nai04012
Entry
nai04012                    Pathway                                
Name
ErbB signaling pathway - Necator americanus (New World hookworm)
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
nai04012  ErbB signaling pathway
nai04012

Organism
Necator americanus (New World hookworm) [GN:nai]
Gene
NECAME_12048  receptor L domain protein [KO:K04361] [EC:2.7.10.1]
NECAME_11673  Phosphatidylinositol-specific phospholipase C, Y domain protein [KO:K01116] [EC:3.1.4.11]
NECAME_05847  hypothetical protein [KO:K04515] [EC:2.7.11.17]
NECAME_04660  CBL proto-oncogene, SH2-like domain protein [KO:K04707] [EC:2.3.2.27]
NECAME_09201  STAT protein, DNA binding domain protein [KO:K11224]
NECAME_07204  putative tyrosine-protein kinase transforming protein Src [KO:K05704] [EC:2.7.10.2]
NECAME_07502  SH3 domain protein [KO:K04438]
NECAME_06130  SH2 domain protein [KO:K06619] [EC:2.7.10.2]
NECAME_01485  hypothetical protein [KO:K19862]
NECAME_08069  kinase domain protein [KO:K04430] [EC:2.7.12.2]
NECAME_02715  kinase domain protein [KO:K04431] [EC:2.7.12.2]
NECAME_13299  hypothetical protein [KO:K04431] [EC:2.7.12.2]
NECAME_10255  kinase domain protein [KO:K04440] [EC:2.7.11.24]
NECAME_05438  SH2 domain protein [KO:K06279]
NECAME_09671  SH3 domain protein [KO:K04364]
NECAME_07252  PH domain protein [KO:K03099]
NECAME_05978  Miro-like protein [KO:K07827]
NECAME_05045  Ras family protein [KO:K07827]
NECAME_16277  kinase domain protein [KO:K04365] [EC:2.7.11.1]
NECAME_05191  kinase domain protein [KO:K04368] [EC:2.7.12.2]
NECAME_10005  kinase domain protein [KO:K04371] [EC:2.7.11.24]
NECAME_10006  Mitogen-activated protein kinase 1 family protein [KO:K04371] [EC:2.7.11.24]
NECAME_06436  kinase domain protein [KO:K04456] [EC:2.7.11.1]
NECAME_09870  kinase domain protein [KO:K04688] [EC:2.7.11.1]
NECAME_10523  kinase domain protein [KO:K03083] [EC:2.7.11.26]
NECAME_03830  hypothetical protein [KO:K03083] [EC:2.7.11.26]
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
nai04010  MAPK signaling pathway
nai04020  Calcium signaling pathway
nai04150  mTOR signaling pathway
KO pathway
ko04012   
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