Cell Signaling Technology

Product Pathways - Tyrosine Kinase/ Adaptors

Phospho-HER2/ErbB2(Tyr1248) Antibody #2247

Applications Reactivity MW (kDa) Source
W H 185 Rabbit

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

Specificity / Sensitivity

Phospho-HER2/ErbB2 (Tyr1248) Antibody detects endogenous levels of ErbB2 only when phosphorylated at tyrosine 1248. The antibody may cross react with EGFR when phosphorylated at tyrosine 1173.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to residues surrounding Tyr1248 of human ErbB2 protein. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of SKBR3 cells untreated or treated with lambda phosphatase using Phospho-Her2 (Tyr 1248) (upper) or Her2/ErbB2 Antibody #2242 (lower).

Western Blotting

Western Blotting

Western blot analysis of MCF-7 cells untreated or treated with Neuregulin (100ng/ml) for 5 minutes, using Phospho-Her2 (Tyr 1248).

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 with the regulation of ErbB2 degradation by the c-Cbl-regulated proteolytic pathway as 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 areTyr1248 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, 6845-6857.
  2. Qian, X. et al. (1994) Proc. Natl. Acad. Sci. USA 91, 1500-1504.
  3. Dittadi, R. and Gion, M. (2000) J. Natl. Cancer Inst. 92, 1443-1444.
  4. Klapper, L.N. et al. (2000) Cancer Res. 60, 3384-3388.
  5. Kwon, Y.K. et al. (1997) J. Neurosci. 17, 8293-8299.

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