Homology

Species predicted to react based on 100% sequence homology: Rat.

Protocols

4290:

Western Blotting,  Immunohistochemistry (Paraffin)

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).

1. Muthuswamy, S.K. et al. (1999) Mol Cell Biol 19, 6845-57.
2. Qian, X. et al. (1994) Proc Natl Acad Sci USA 91, 1500-4.
3. Dittadi, R. and Gion, M. (2000) J Natl Cancer Inst 92, 1443-4.
4. Klapper, L.N. et al. (2000) Cancer Res 60, 3384-8.
5. Kwon, Y.K. et al. (1997) J Neurosci 17, 8293-9.

Application References

• Kuroda, A. et al. (2011) PLoS One 6, e22313. Applications: IHC-P (paraffin).

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Companion Products

• 7074  Anti-rabbit IgG, HRP-linked Antibody
• 7727  Biotinylated Protein Ladder Detection Pack
• 2165  HER2/ErbB2 (29D8) Rabbit mAb
• 2248  HER2/ErbB2 (44E7) Mouse mAb
• 3250  HER2/ErbB2 (M45) Antibody
• 2242  HER2/ErbB2 Antibody
• 6942  Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb
• 2243  Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
• 2249  Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
• 2247  Phospho-HER2/ErbB2 (Tyr1248) Antibody
• 2244  Phospho-HER2/ErbB2 (Tyr1248)/EGFR (Tyr1173) Antibody
• 2241  Phospho-HER2/ErbB2 (Tyr877) Antibody
• 9923  Phospho-HER2/ErbB2 Antibody Sampler Kit
• 6883  SignalFire™ ECL Reagent
• 12757  SignalFire™ Elite ECL Reagent
• 12630  SignalFire™ Plus ECL Reagent
• 8117  SignalSlide^® Phospho-ErbB Family IHC Controls
• 8112  SignalStain^® Antibody Diluent
• 8114  SignalStain^® Boost IHC Detection Reagent (HRP, Rabbit)

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