receptor tyrosine-protein kinase erbB-2; p185erbB2; C-erbB-2; NEU proto-oncogene; tyrosine kinase-type cell surface receptor HER2; MLN 19; CD340 (ERBB2, HER2, NEU, NGL)
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Function
- essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone
- GP30 is a potential ligand for this receptor
- not activated by EGF, TGF-alpha & amphiregulin
- heterodimer with each of the other ERBB receptors (putative)
- interacts with PRKCABP & PLXNB1
- part of a complex with EGFR & either PIK3C2A or PIK3C2B
- may interact with PIK3C2B when phosphorylated on Tyr-1196
- interacts with MEMO when phosphorylated on Tyr-1248
- interacts with MUC1
- ligand-binding increases phosphorylation on Tyr
- component of IL-6 signalling through MAPK pathway
- can activate the phosphatidylinositol 3 kinase/ AKT1 kinase pathway.
Structure
- belongs to the protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily
- contains 1 protein kinase domain
Compartment
membrane
Pathology
- overexpressed in 20-30% of breast & ovarian cancers
- overexpression increases aggressiveness & confers taxol resistance in breast cancers
- ERBB2 can phosphorylate & activate the estrogen receptor in the absence of estrogen
- stimulation by heregulin (HRG) in breast cancer cell lines induces binding of MUC1 with gamma-catenin
- overexpressed in gastroesophageal junction cancer
Polymorphism
- 4 alleles due to the variations in positions 654 & 655
- allele B1 (Ile-654/Ile-655) has a frequency of 0.782
- allele B2 (Ile-654/Val-655) has a frequency of 0.206
- allele B3 (Val-654/Val-655) has a frequency of 0.012
Pharmacology
- HER2 monoclonal antibody trastuzumab active in cancers overexpressing HER2-neu protein
Laboratory
- measurement of HER2/Neu protein_expression in patients with breast cancer has prognostic value
More general terms
Additional terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P04626.html
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/ERBB2ID162ch17q11.html
- ↑ Wikipedia; ERBB2 entry http://en.wikipedia.org/wiki/ERBB2
- ↑ Molecular Cell Biology (2nd ed) Darnell J; Lodish H & Baltimore D (eds), Scientific American Books, WH Freeman, NY 1990, pg 986
- ↑ Lupu R, Colomer R, Zugmaier G, Sarup J, Shepard M, Slamon D, Lippman ME. Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. Science. 1990 Sep 28;249(4976):1552-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2218496
- ↑ Yarden & Ullrich Ann Rev Biochem 57:443 1988
- ↑ Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281-302. Review. Erratum in: Cell 1991 May 31;65(5):following 914. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1846320
- ↑ Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, Yansura D, Abadi N, Raab H, Lewis GD, et al. Identification of heregulin, a specific activator of p185erbB2. Science. 1992 May 22;256(5060):1205-10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1350381
- ↑ Marchionni MA, Goodearl AD, Chen MS, Bermingham-McDonogh O, Kirk C, Hendricks M, Danehy F, Misumi D, Sudhalter J, Kobayashi K, et al. Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature. 1993 Mar 25;362(6418):312-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8096067
- ↑ Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001 Oct;1(1):34-45. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11900250
Patient information
neu proto-oncogene protein (p185neu), her2/neu or erbB-2 protein