Entry Name ErbB signaling pathway - Molossus molossus (Pallas's mastiff bat)
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 transductionBRITE hierarchy 
Pathway map Organism Molossus molossus (Pallas's mastiff bat) [GN:
mmf ]
Gene 118615118   CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ] 
118615659   NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456 ] 
118616460   PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ] 
118617106   PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ] 
118618299   PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ] 
118619531   CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ] 
118622312   NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455 ] 
118622710   EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ] 
118626944   PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ] 
118632208   NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457 ] 
118632270   CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ] 
118632927   PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ] 
118634401   STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224 ] 
118636653   ELK1; LOW QUALITY PROTEIN: ETS domain-containing protein Elk-1 [KO:K04375 ] 
118642883   PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ] 
118643618   CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ] 
Compound 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 Reference   Authors Yarden Y, Sliwkowski MX.
  Title Untangling the ErbB signalling network.
  Journal Reference   Authors Citri A, Yarden Y.
  Title EGF-ERBB signalling: towards the systems level.
  Journal Reference   Authors Scaltriti M, Baselga J.
  Title The epidermal growth factor receptor pathway: a model for targeted therapy.
  Journal 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 Reference   Authors Holbro T, Hynes NE.
  Title ErbB receptors: directing key signaling networks throughout life.
  Journal Reference   Authors Liang J, Slingerland JM.
  Title Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.
  Journal Reference   Authors Hynes NE, Lane HA.
  Title ERBB receptors and cancer: the complexity of targeted inhibitors.
  Journal Reference   Authors Oda K, Matsuoka Y, Funahashi A, Kitano H.
  Title A comprehensive pathway map of epidermal growth factor receptor signaling.
  Journal Reference   Authors Schulze WX, Deng L, Mann M.
  Title Phosphotyrosine interactome of the ErbB-receptor kinase family.
  Journal Reference   Authors Olayioye MA, Neve RM, Lane HA, Hynes NE.
  Title The ErbB signaling network: receptor heterodimerization in development and cancer.
  Journal Reference   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 Reference   Authors Muthuswamy SK, Gilman M, Brugge JS.
  Title Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
  Journal Reference   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 Related KO pathway