Entry Name ErbB signaling pathway - Danio rerio (zebrafish)
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 Danio rerio (zebrafish) [GN:
dre ]
Gene 403045 egf; pro-epidermal growth factor isoform 1 precursor [KO:K04357 ]
373867 plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116 ] [EC:3.1.4.11 ]
561747 plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859 ] [EC:3.1.4.11 ]
436815 camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain [KO:K04515 ] [EC:2.7.11.17 ]
445208 camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform 1 [KO:K04515 ] [EC:2.7.11.17 ]
550436 camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2 [KO:K04515 ] [EC:2.7.11.17 ]
562064 camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 [KO:K04515 ] [EC:2.7.11.17 ]
793359 camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X26 [KO:K04515 ] [EC:2.7.11.17 ]
798222 camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X4 [KO:K04515 ] [EC:2.7.11.17 ]
791855 camk2g1; calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma 1 [KO:K04515 ] [EC:2.7.11.17 ]
369197 stat5a; signal transducer and activator of transcription 5A [KO:K11224 ]
445474 stat5b; signal transducer and activator of transcription 5B [KO:K11224 ]
403052 map2k4a; dual specificity mitogen-activated protein kinase kinase 4a [KO:K04430 ] [EC:2.7.12.2 ]
568951 map2k4b; dual specificity mitogen-activated protein kinase kinase 4b [KO:K04430 ] [EC:2.7.12.2 ]
567895 elk1; ETS domain-containing protein Elk-1 [KO:K04375 ]
797938 hbegfa; heparin-binding EGF-like growth factor a precursor [KO:K08523 ]
407664 hbegfb; heparin-binding EGF-like growth factor b precursor [KO:K08523 ]
796461 nrg1; pro-neuregulin-1, membrane-bound isoform isoform 1 [KO:K05455 ]
323818 shc1; SHC-transforming protein 1 isoform X3 [KO:K06279 ]
406308 grb2b; growth factor receptor-bound protein 2b [KO:K04364 ]
493609 grb2a; growth factor receptor-bound protein 2a [KO:K04364 ]
563181 map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369 ] [EC:2.7.12.2 ]
30686 myca; transcriptional regulator Myc-A [KO:K04377 ]
101882495 nrg3b; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457 ]
394174 pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
561737 pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100002263 pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
404211 pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100000252 pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) [KO:K02649 ]
557176 pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
799566 eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
58100 badb; BCL2 associated agonist of cell death b isoform 1 [KO:K02158 ]
564921 bada; bcl2-associated agonist of cell death isoform X1 [KO:K02158 ]
368329 cdkn1bb; cyclin dependent kinase inhibitor 1Bb [KO:K06624 ]
402862 cdkn1ba; cyclin-dependent kinase inhibitor 1Ba [KO:K06624 ]
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
