ErbB signaling pathway (WP673)

Homo sapiens

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The ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's Disease. In mice loss of signaling by any member of the ErbB family results in embryonic lethality with defects in organs including the lungs, skin, heart and brain. Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB-1 and ErbB-2 are found in many human cancers and their excessive signaling may be critical factors in the development and malignancy of these tumors. The ErbB protein family consists of 4 members * ErbB-1, also named epidermal growth factor receptor (EGFR) * ErbB-2, also named HER2 in humans and neu in rodents * ErbB-3, also named HER3 and * ErbB-4, also named HER4 The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher order oligomers upon activation by a subset of potential growth factor ligands. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP673 CPTAC Assay Portal]

Authors

Luigi Maiorana , Kristina Hanspers , Alex Pico , Christine Chichester , Egon Willighagen , Martina Summer-Kutmon , Eric Jaehnig , Friederike Ehrhart , Lauren J. Dupuis , Eric Weitz , and Finterly Hu

Activity

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC ExRNA PancCanNet

Annotations

Disease Ontology

cancer Alzheimer's disease multiple sclerosis

Pathway Ontology

epidermal growth factor/neuregulin signaling pathway oxidative phosphorylation pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
IP3 Metabolite chebi:16595
PIP3 Metabolite hmdb:HMDB0004249
Ca2+ Metabolite chebi:29108
Diacylglycerol Metabolite chebi:18035
PIP2 Metabolite chebi:18348
PIK3CA GeneProduct ncbigene:5290
MAPK10 GeneProduct ncbigene:5602
RPS6KB2 GeneProduct ncbigene:6199
AKT1 GeneProduct ncbigene:207
AKT2 GeneProduct ncbigene:208
SHC2 GeneProduct ncbigene:25759
PLCG2 GeneProduct ncbigene:5336
GSK3B GeneProduct ensembl:ENSG00000082701
NRG4 GeneProduct ncbigene:145957
MDM2 GeneProduct ncbigene:4193
PIK3R3 GeneProduct ncbigene:8503
ERBB4 GeneProduct ncbigene:2066
AKT3 GeneProduct ncbigene:10000
PLCG1 GeneProduct ncbigene:5335
BTC GeneProduct ncbigene:685
MAPK8 GeneProduct ncbigene:5599
p53 GeneProduct ncbigene:7157
ERBB3 GeneProduct ncbigene:2065
NRG1 GeneProduct ncbigene:3084
EGFR GeneProduct ncbigene:1956
ERBB2 GeneProduct ncbigene:2064
MYC GeneProduct ncbigene:4609
BAD GeneProduct ncbigene:572
AREG GeneProduct ncbigene:374
GAB1 GeneProduct ncbigene:2549
ELK1 GeneProduct ncbigene:2002
TGFA GeneProduct ncbigene:7039
SOS1 GeneProduct ncbigene:6654
ERBB2 GeneProduct ncbigene:2064
SRC GeneProduct ncbigene:6714
BIM GeneProduct ncbigene:10018
GRB2 GeneProduct ncbigene:2885
NRG3 GeneProduct ncbigene:10718
EREG GeneProduct ncbigene:2069
ERBB2 GeneProduct ncbigene:2064
GRB2 GeneProduct ncbigene:2885
MYC GeneProduct ncbigene:4609
CDKN1A GeneProduct ncbigene:1026
JUN GeneProduct ncbigene:3725
ERBB4 GeneProduct ncbigene:2066
HBEGF GeneProduct ncbigene:1839
EGF GeneProduct ncbigene:1950
EIF4EBP1 GeneProduct ncbigene:1978
ERBB2 GeneProduct ncbigene:2064
EGFR GeneProduct ncbigene:1956
CRK GeneProduct ncbigene:1398
ERBB2 GeneProduct ncbigene:2064
ERBB4 GeneProduct ncbigene:2066
ERBB3 GeneProduct ncbigene:2065
PRKCA GeneProduct ncbigene:5578
p27 GeneProduct ncbigene:1027
CAMK2A GeneProduct ncbigene:815
PDPK1 GeneProduct ensembl:ENSG00000140992
MTOR GeneProduct ncbigene:2475
HRAS GeneProduct ncbigene:3265
STAT5A GeneProduct ncbigene:6776
KRAS GeneProduct ncbigene:3845
CBL GeneProduct ncbigene:867
CCND1 GeneProduct ncbigene:595
PAK4 GeneProduct ncbigene:10298
NCK1 GeneProduct ncbigene:4690
MAP2K7 GeneProduct ncbigene:5609
EGFR GeneProduct ncbigene:1956
ERBB3 GeneProduct ncbigene:2065
PTK2 GeneProduct ncbigene:5747
ABL1 GeneProduct ncbigene:25
NRG2 GeneProduct ncbigene:9542
FOXO1 GeneProduct ncbigene:2308
ELK1 GeneProduct ncbigene:2002
CAMK2B GeneProduct ncbigene:816
CAMK2D GeneProduct ncbigene:817
CAMK2G GeneProduct ncbigene:818
PRKCB GeneProduct ncbigene:5579
PRKCG GeneProduct ncbigene:5582
CBLB GeneProduct ncbigene:868
STAT5B GeneProduct ncbigene:6777
CRKL GeneProduct ncbigene:1399
ABL2 GeneProduct ncbigene:27
NCK2 GeneProduct ncbigene:8440
PAK1 GeneProduct ncbigene:5058
PAK2 GeneProduct ncbigene:5062
PAK3 GeneProduct ncbigene:5063
PAK5 GeneProduct ncbigene:57144
PAK6 GeneProduct ncbigene:56924
BUB1B-PAK6 GeneProduct ncbigene:106821730
MAP2K4 GeneProduct ncbigene:6416
MAPK9 GeneProduct ncbigene:5601
SHC3 GeneProduct ncbigene:53358
SHC4 GeneProduct ncbigene:399694
SHC1 GeneProduct ncbigene:6464
SOS2 GeneProduct ncbigene:6655
NRAS GeneProduct ncbigene:4893
STAT5A GeneProduct ncbigene:6776
STAT5B GeneProduct ncbigene:6777
PIK3R2 GeneProduct ncbigene:5296
PIK3R1 GeneProduct ncbigene:5295
PIK3CD GeneProduct ncbigene:5293
PIK3CB GeneProduct ncbigene:5291
RPS6KB1 GeneProduct ncbigene:6198
ARAF GeneProduct ensembl:ENSG00000078061
BRAF GeneProduct ncbigene:673
RAF1 GeneProduct ncbigene:5894
MAP2K1 GeneProduct ncbigene:5604
MAPK1 GeneProduct ncbigene:5594
MAPK3 GeneProduct ncbigene:5595
MAP2K2 GeneProduct ncbigene:5605

References

  1. Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor. Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, et al. J Biol Chem. 1998 Jul 3;273(27):17186–91. PubMed Europe PMC Scholia
  2. The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events. McCarty JH. Bioessays. 1998 Nov;20(11):913–21. PubMed Europe PMC Scholia
  3. Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Muthuswamy SK, Gilman M, Brugge JS. Mol Cell Biol. 1999 Oct;19(10):6845–57. PubMed Europe PMC Scholia
  4. The ErbB signaling network: receptor heterodimerization in development and cancer. Olayioye MA, Neve RM, Lane HA, Hynes NE. EMBO J. 2000 Jul 3;19(13):3159–67. PubMed Europe PMC Scholia
  5. Untangling the ErbB signalling network. Yarden Y, Sliwkowski MX. Nat Rev Mol Cell Biol. 2001 Feb;2(2):127–37. PubMed Europe PMC Scholia
  6. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Liang J, Slingerland JM. Cell Cycle. 2003;2(4):339–45. PubMed Europe PMC Scholia
  7. ErbB receptors: directing key signaling networks throughout life. Holbro T, Hynes NE. Annu Rev Pharmacol Toxicol. 2004;44:195–217. PubMed Europe PMC Scholia
  8. Signal transduction and oncogenesis by ErbB/HER receptors. Marmor MD, Skaria KB, Yarden Y. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):903–13. PubMed Europe PMC Scholia
  9. ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events. Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, et al. J Biol Chem. 2005 Jun 24;280(25):24175–80. PubMed Europe PMC Scholia
  10. ERBB receptors and cancer: the complexity of targeted inhibitors. Hynes NE, Lane HA. Nat Rev Cancer. 2005 May;5(5):341–54. PubMed Europe PMC Scholia
  11. Epidermal growth factor receptor (EGFR) signaling in cancer. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Gene. 2006 Jan 17;366(1):2–16. PubMed Europe PMC Scholia
  12. Phosphotyrosine interactome of the ErbB-receptor kinase family. Schulze WX, Deng L, Mann M. Mol Syst Biol. 2005;1:2005.0008. PubMed Europe PMC Scholia
  13. A comprehensive pathway map of epidermal growth factor receptor signaling. Oda K, Matsuoka Y, Funahashi A, Kitano H. Mol Syst Biol. 2005;1:2005.0010. PubMed Europe PMC Scholia
  14. EGF-ERBB signalling: towards the systems level. Citri A, Yarden Y. Nat Rev Mol Cell Biol. 2006 Jul;7(7):505–16. PubMed Europe PMC Scholia
  15. The epidermal growth factor receptor pathway: a model for targeted therapy. Scaltriti M, Baselga J. Clin Cancer Res. 2006 Sep 15;12(18):5268–72. PubMed Europe PMC Scholia
  16. Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion. Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A, et al. J Biol Chem. 2009 Jul 3;284(27):18515–24. PubMed Europe PMC Scholia
  17. Case records of the Massachusetts General Hospital. Case 19-2010. A 35-year-old man with adenocarcinoma of the cecum. Ryan DP, Engelman JA, Ferrone CR, Sahani DV, Lisovsky M. N Engl J Med. 2010 Jun 24;362(25):2411–9. PubMed Europe PMC Scholia
  18. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia