Entry Name ErbB signaling pathway - Orcinus orca (killer whale)
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 Ortholog table Organism Orcinus orca (killer whale) [GN:
oor ]
Gene 101281412 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
101269181 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X16 [KO:K04515 ] [EC:2.7.11.17 ]
101287513 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515 ] [EC:2.7.11.17 ]
101281498 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X8 [KO:K04515 ] [EC:2.7.11.17 ]
101271879 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
101280792 STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223 ]
101280265 STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224 ]
101276475 NRG1; pro-neuregulin-1, membrane-bound isoform isoform X2 [KO:K05455 ]
101274058 NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456 ]
101287317 NRG3; pro-neuregulin-3, membrane-bound isoform isoform X4 [KO:K05457 ]
101278075 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101278974 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
101283011 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101277568 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101285437 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101281352 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649 ]
101277165 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
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 LinkDB All DBs
