Entry Name ErbB signaling pathway - Mus musculus (house mouse)
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 Mus musculus (house mouse) [GN:
mmu ]
Gene 12015 Bad; BCL2-associated agonist of cell death [KO:K02158 ]
12223 Btc; betacellulin, epidermal growth factor family member [KO:K09783 ]
12575 Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
12576 Cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624 ]
12928 Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438 ]
12929 Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438 ]
13685 Eif4ebp1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205 ]
13712 Elk1; ELK1, member of ETS oncogene family [KO:K04375 ]
14388 Gab1; growth factor receptor bound protein 2-associated protein 1 [KO:K09593 ]
14784 Grb2; growth factor receptor bound protein 2 [KO:K04364 ]
15200 Hbegf; heparin-binding EGF-like growth factor [KO:K08523 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
17973 Nck1; non-catalytic region of tyrosine kinase adaptor protein 1 [KO:K07365 ]
17974 Nck2; non-catalytic region of tyrosine kinase adaptor protein 2 [KO:K19862 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
20416 Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279 ]
20418 Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448 ]
20662 Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
20663 Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
20850 Stat5a; signal transducer and activator of transcription 5A [KO:K11223 ]
20851 Stat5b; signal transducer and activator of transcription 5B [KO:K11224 ]
216148 Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447 ]
21802 Tgfa; transforming growth factor alpha [KO:K08774 ]
271849 Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
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
