Entry Name ErbB signaling pathway - Cyclopterus lumpus (lumpfish)
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 Cyclopterus lumpus (lumpfish) [GN:
clum ]
Gene 117730534 tgfa; LOW QUALITY PROTEIN: protransforming growth factor alpha [KO:K08774 ]
117731103 camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
117736189 camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
117742710 camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
117743645 camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
117747815 camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
117748445 signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224 ]
117734568 stat5a; signal transducer and activator of transcription 5A [KO:K11224 ]
117735077 map2k4a; dual specificity mitogen-activated protein kinase kinase 4a isoform X1 [KO:K04430 ] [EC:2.7.12.2 ]
117740649 june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
117738045 hbegfa; heparin-binding EGF-like growth factor a isoform X1 [KO:K08523 ]
117746647 map2k2b; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369 ] [EC:2.7.12.2 ]
117732996 pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
117729144 pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
117741125 pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
117747650 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
117736025 phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649 ]
117740185 pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
117746515 phosphatidylinositol 3-kinase regulatory subunit gamma-like isoform X1 [KO:K02649 ]
117729683 pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649 ]
117729698 phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649 ]
117746960 pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
117736949 eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205 ]
117740409 eukaryotic translation initiation factor 4E-binding protein 1-like isoform X1 [KO:K07205 ]
117731143 cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625 ]
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
