ErbB signaling pathway - Homo sapiens (human)
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.
Environmental Information Processing; Signal transduction
Pathway map Ortholog table
N00021 EGF-ERBB2-RAS-ERK signaling pathway
N00231 TGFA-EGFR-PI3K signaling pathway
N01163 NRG-ERBB4-PI3K signaling pathway
D01977 Gefitinib (JP18/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)
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)
D11991 Zenocutuzumab (USAN/INN)
D12001 Mobocertinib (USAN/INN)
D12184 Patritumab deruxtecan (INN)
D12230 Poziotinib hydrochloride (USAN)
D12245 Lazertinib mesilate hydrate (JAN)
D12259 Aumolertinib mesylate (USAN)
D12416 Petosemtamab (USAN/INN)
D12444 Nilotinib hydrochloride dihydrate (JAN)
D12457 Tuxobertinib (USAN/INN)
Homo sapiens (human) [GN:
7039 TGFA; transforming growth factor alpha [KO: K08774]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO: K04515] [EC: 18.104.22.168]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO: K04515] [EC: 22.214.171.124]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO: K04515] [EC: 126.96.36.199]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO: K04515] [EC: 188.8.131.52]
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: 184.108.40.206]
27 ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO: K08887] [EC: 220.127.116.11]
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: 18.104.22.168]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 22.214.171.124]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 126.96.36.199]
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]
C01245 D-myo-Inositol 1,4,5-trisphosphate
Marmor MD, Skaria KB, Yarden Y.
Signal transduction and oncogenesis by ErbB/HER receptors.
Yarden Y, Sliwkowski MX.
Untangling the ErbB signalling network.
Citri A, Yarden Y.
EGF-ERBB signalling: towards the systems level.
Scaltriti M, Baselga J.
The epidermal growth factor receptor pathway: a model for targeted therapy.
Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS.
Epidermal growth factor receptor (EGFR) signaling in cancer.
Holbro T, Hynes NE.
ErbB receptors: directing key signaling networks throughout life.
Liang J, Slingerland JM.
Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.
Hynes NE, Lane HA.
ERBB receptors and cancer: the complexity of targeted inhibitors.
Oda K, Matsuoka Y, Funahashi A, Kitano H.
A comprehensive pathway map of epidermal growth factor receptor signaling.
Schulze WX, Deng L, Mann M.
Phosphotyrosine interactome of the ErbB-receptor kinase family.
Olayioye MA, Neve RM, Lane HA, Hynes NE.
The ErbB signaling network: receptor heterodimerization in development and cancer.
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.
Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE.
ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.
Muthuswamy SK, Gilman M, Brugge JS.
Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M.
Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.