Entry Name ErbB signaling pathway
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 Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02158 BAD; Bcl-2-antagonist of cell death
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04357 EGF; epidermal growth factor
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04375 ELK1; ETS domain-containing protein Elk-1
K04377 MYC; Myc proto-oncogene protein
K04430 MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04438 CRK, CRKII; C-crk adapter molecule crk
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 JUN; transcription factor AP-1
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K05083 ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1 ]
K05084 ERBB3, HER3; receptor tyrosine-protein kinase erbB-3 [EC:2.7.10.1 ]
K05085 ERBB4, HER4; receptor tyrosine-protein kinase erbB-4 [EC:2.7.10.1 ]
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K06279 SHC1; SHC-transforming protein 1
K06624 CDKN1B, P27, KIP1; cyclin-dependent kinase inhibitor 1B
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07205 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1
K07365 NCK1; NCK adaptor protein 1
K07827 KRAS, KRAS2; GTPase KRas
K08523 HBEGF; heparin-binding EGF-like growth factor
K08774 TGFA; transforming growth factor, alpha
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09593 GAB1; GRB2-associated-binding protein 1
K11223 STAT5A; signal transducer and activator of transcription 5A
K11224 STAT5B; signal transducer and activator of transcription 5B
K17447 SHC2; SHC-transforming protein 2
K17448 SHC3; SHC-transforming protein 3
K17449 SHC4; SHC-transforming protein 4
K19862 NCK2, GRB4; NCK adaptor protein 2
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
