WB, IP
H M
Endogenous
185
Rabbit IgG
#P04626
2064
Product Information
Product Usage Information
| Application | Dilution |
|---|---|
| Western Blotting | 1:1000 |
| Immunoprecipitation | 1:100 |
Storage
Specificity / Sensitivity
Species Reactivity:
Human, Mouse
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1196 of human HER2/ErbB2 protein.
Background
The ErbB2 (HER2) proto-oncogene encodes a 185 kDa transmembrane, receptor-like glycoprotein with intrinsic tyrosine kinase activity (1). While ErbB2 lacks an identified ligand, ErbB2 kinase activity can be activated in the absence of a ligand when overexpressed and through heteromeric associations with other ErbB family members (2). Amplification of the ErbB2 gene and overexpression of its product are detected in almost 40% of human breast cancers (3). Binding of the c-Cbl ubiquitin ligase to ErbB2 at Tyr1112 leads to ErbB2 poly-ubiquitination and enhances degradation of this kinase (4). ErbB2 is a key therapeutic target in the treatment of breast cancer and other carcinomas and targeting the regulation of ErbB2 degradation by the c-Cbl-regulated proteolytic pathway is one potential therapeutic strategy. Phosphorylation of the kinase domain residue Tyr877 of ErbB2 (homologous to Tyr416 of pp60c-Src) may be involved in regulating ErbB2 biological activity. The major autophosphorylation sites in ErbB2 are Tyr1248 and Tyr1221/1222; phosphorylation of these sites couples ErbB2 to the Ras-Raf-MAP kinase signal transduction pathway (1,5).
The autophosphorylation of HER/ErbB2 at Tyr1196 mediates HER2/ErbB2 association with Crk protein and leads to Ras-independent downstream Erk acitvation (6). HER2/ErbB2 phosphorylation at Tyr1196 has been coupled to cell migration and polarity disruption (7,8).
- Muthuswamy, S.K. et al. (1999) Mol Cell Biol 19, 6845-57.
- Qian, X. et al. (1994) Proc Natl Acad Sci USA 91, 1500-4.
- Dittadi, R. and Gion, M. (2000) J Natl Cancer Inst 92, 1443-4.
- Klapper, L.N. et al. (2000) Cancer Res 60, 3384-8.
- Kwon, Y.K. et al. (1997) J Neurosci 17, 8293-9.
- Dankort, D. et al. (2001) Mol Cell Biol 21, 1540-51.
- Marone, R. et al. (2004) Nat Cell Biol 6, 515-22.
- Lucs, A.V. et al. (2010) Oncogene 29, 174-87.
Species Reactivity
Species reactivity is determined by testing in at least one approved application (e.g., western blot).
Western Blot Buffer
IMPORTANT: For western blots, incubate membrane with diluted primary antibody in 5% w/v nonfat dry milk, 1X TBS, 0.1% Tween® 20 at 4°C with gentle shaking, overnight.
Applications Key
WB: Western Blotting IP: Immunoprecipitation
Cross-Reactivity Key
H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected
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