Cell Signaling Technology

Product Pathways - Tyrosine Kinase / Adaptors

Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb #6942

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H Endogenous 185 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Phospho-HER2/ErbB2 (Tyr1196) D66B7) Rabbit mAb recognizes endogenous levels of HER2/ErbB2 protein only when phosphorylated at Tyr1196. The antibody may detect other activated ErbB family members.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1196 of human HER2/ErbB2 protein.

Western Blotting

Western Blotting

Western blot analysis of extracts from T47D and MCF7 cells, untreated or treated with human neuregulin-1 #5218 (100 ng/ml, 5 min), using Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb (upper) and HER2/ErbB2 (29D8) Rabbit mAb #2165 (lower).

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).

  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.
  6. Dankort, D. et al. (2001) Mol Cell Biol 21, 1540-51.
  7. Marone, R. et al. (2004) Nat Cell Biol 6, 515-22.
  8. Lucs, A.V. et al. (2010) Oncogene 29, 174-87.

Application References

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For Research Use Only. Not For Use In Diagnostic Procedures.

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