Entry
Name
ErbB signaling pathway - Takifugu rubripes (torafugu)
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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Organism
Takifugu rubripes (torafugu) [GN:
tru ]
Gene
101062260 camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
101072713 hbegf; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523 ]
101075752 pro-neuregulin-2, membrane-bound isoform-like isoform X1 [KO:K05456 ]
101061204 growth factor receptor-bound protein 2-like isoform X2 [KO:K04364 ]
115249620 pro-neuregulin-3, membrane-bound isoform-like isoform X1 [KO:K05457 ]
115252028 pro-neuregulin-3, membrane-bound isoform-like isoform X1 [KO:K05457 ]
101066265 nrg4; pro-neuregulin-4, membrane-bound isoform isoform X1 [KO:K05458 ]
101068840 pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
101066166 pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101072152 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101076867 pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
101065244 phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649 ]
101079698 phosphatidylinositol 3-kinase regulatory subunit beta-like isoform X1 [KO:K02649 ]
101061527 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
101063692 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
101077380 pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101062512 phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649 ]
101071696 eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205 ]
101079890 eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205 ]
115246466 eukaryotic translation initiation factor 4E-binding protein 1-like [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 pathway
KO pathway
LinkDB
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