Entry |
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Name |
ErbB signaling pathway - Homo sapiens (human)
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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.
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Class |
Environmental Information Processing; Signal transduction
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Pathway map |

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Network |
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Element |
N00021 | EGF-ERBB2-RAS-ERK signaling pathway |
N00231 | TGFA-EGFR-PI3K signaling pathway |
N01163 | NRG-ERBB4-PI3K signaling pathway |
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Disease |
H00931 | Growth hormone insensitivity with immunodeficiency |
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Drug |
D01977 | Gefitinib (JAN/USAN/INN) |
D02714 | Everolimus (JAN/USAN/INN) |
D03350 | Canertinib dihydrochloride (USAN) |
D04023 | Erlotinib hydrochloride (JAN/USAN) |
D04024 | Lapatinib ditosylate (USAN) |
D06068 | Temsirolimus (JAN/USAN/INN) |
D06272 | Sorafenib tosylate (USAN) |
D06407 | Vandetanib (JAN/USAN/INN) |
D06413 | Nilotinib hydrochloride hydrate (JAN) |
D08344 | Tozasertib lactate (USAN) |
D09665 | Saracatinib difumarate (USAN) |
D09690 | Varlitinib tosylate (USAN) |
D09728 | Bosutinib hydrate (JAN) |
D09733 | Afatinib dimaleate (USAN) |
D09980 | Trastuzumab emtansine (USAN/INN) |
D09996 | Vemurafenib (JAN/USAN/INN) |
D10104 | Dabrafenib mesylate (USAN) |
D10176 | Trametinib dimethyl sulfoxide (JAN/USAN) |
D10486 | Pimasertib hydrochloride (USAN) |
D10766 | Osimertinib mesylate (USAN) |
D11053 | Encorafenib (JAN/USAN/INN) |
D11115 | Olmutinib hydrochloride (USAN) |
D11239 | Lumretuzumab (USAN/INN) |
D11411 | Lifirafenib maleate (USAN) |
D11434 | Nazartinib mesylate (USAN) |
D11529 | Trastuzumab deruxtecan (USAN/INN) |
D11691 | Tirbanibulin (USAN/INN) |
D11692 | Tirbanibulin mesylate (USAN) |
D11777 | Seribantumab (USAN/INN) |
D11803 | Cetuximab sarotalocan (USAN/INN) |
D11805 | Cetuximab sarotalocan sodium (genetical recombination) (JAN) |
D11874 | Serclutamab talirine (USAN/INN) |
D11969 | Mobocertinib succinate (JAN) |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
7039 | TGFA; transforming growth factor alpha [KO:K08774] |
815 | CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17] |
817 | CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17] |
816 | CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17] |
818 | CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17] |
6776 | STAT5A; signal transducer and activator of transcription 5A [KO:K11223] |
6777 | STAT5B; signal transducer and activator of transcription 5B [KO:K11224] |
1398 | CRK; CRK proto-oncogene, adaptor protein [KO:K04438] |
1399 | CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438] |
25 | ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2] |
27 | ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:2.7.10.2] |
3725 | JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448] |
2002 | ELK1; ETS transcription factor ELK1 [KO:K04375] |
1839 | HBEGF; heparin binding EGF like growth factor [KO:K08523] |
2885 | GRB2; growth factor receptor bound protein 2 [KO:K04364] |
6654 | SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099] |
6655 | SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099] |
3265 | HRAS; HRas proto-oncogene, GTPase [KO:K02833] |
3845 | KRAS; KRAS proto-oncogene, GTPase [KO:K07827] |
4893 | NRAS; NRAS proto-oncogene, GTPase [KO:K07828] |
4609 | MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377] |
2549 | GAB1; GRB2 associated binding protein 1 [KO:K09593] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
1978 | EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205] |
572 | BAD; BCL2 associated agonist of cell death [KO:K02158] |
1027 | CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624] |
1026 | CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Marmor MD, Skaria KB, Yarden Y. |
Title |
Signal transduction and oncogenesis by ErbB/HER receptors. |
Journal |
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Reference |
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Authors |
Yarden Y, Sliwkowski MX. |
Title |
Untangling the ErbB signalling network. |
Journal |
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Reference |
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Authors |
Citri A, Yarden Y. |
Title |
EGF-ERBB signalling: towards the systems level. |
Journal |
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Reference |
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Authors |
Scaltriti M, Baselga J. |
Title |
The epidermal growth factor receptor pathway: a model for targeted therapy. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Holbro T, Hynes NE. |
Title |
ErbB receptors: directing key signaling networks throughout life. |
Journal |
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Reference |
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Authors |
Liang J, Slingerland JM. |
Title |
Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. |
Journal |
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Reference |
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Authors |
Hynes NE, Lane HA. |
Title |
ERBB receptors and cancer: the complexity of targeted inhibitors. |
Journal |
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Reference |
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Authors |
Oda K, Matsuoka Y, Funahashi A, Kitano H. |
Title |
A comprehensive pathway map of epidermal growth factor receptor signaling. |
Journal |
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Reference |
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Authors |
Schulze WX, Deng L, Mann M. |
Title |
Phosphotyrosine interactome of the ErbB-receptor kinase family. |
Journal |
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Reference |
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Authors |
Olayioye MA, Neve RM, Lane HA, Hynes NE. |
Title |
The ErbB signaling network: receptor heterodimerization in development and cancer. |
Journal |
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Reference |
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Authors |
McCarty JH. |
Title |
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Muthuswamy SK, Gilman M, Brugge JS. |
Title |
Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. |
Journal |
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Reference |
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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 |
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Related pathway |
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KO pathway |
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LinkDB |
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