Cell Signaling Technology

Product Pathways - Tyrosine Kinase/ Adaptors

Phospho-HER3/ErbB3 (Tyr1197) (C56E4) Rabbit mAb #4561

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

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human
Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

Phospho-HER3/ErbB3 (Tyr1197) (C56E4) Rabbit mAb detects endogenous levels of HER3/ErbB3 protein only when phosphorylated at Tyr1197. The antibody does not cross-react with other phosphorylated receptor tyrosine kinases.

Source / Purification

Monoclonal antibody is produced by immunizing rabbits with a synthetic phosphopeptide (KLH-coupled) corresponding to residues surrounding Tyr1197 of human HER3/ErbB3.

Western Blotting

Western Blotting

Western blot analysis of extracts from T47D cells, untreated or treated with neuregulin (NRG), using Phospho-HER3/ErbB3 (Tyr1197) (C56E4) Rabbit mAb (upper) and HER3/ErbB3 (1B2) Rabbit mAb #4754 (lower).

Background

HER3/ErbB3 is a member of the ErbB receptor protein tyrosine kinase family, but lacks tyrosine kinase activity. Tyrosine phosphorylation of ErbB3 depends on its association with other ErbB tyrosine kinases. Upon ligand binding, heterodimers form between ErbB3 and other ErbB proteins and ErbB3 is phosphorylated on tyrosine residues by the activated ErbB kinase (1,2). There are at least 9 potential tyrosine phosphorylation sites in the carboxy-terminal tail of ErbB3. These sites serve as consensus binding sites for signal transducing proteins, including Src family members, Grb2 and the p85 subunit of PI3 kinase, which mediate ErbB-downstream signaling (3). Both Tyr1222 and Tyr1289 of ErbB3 reside within a YXXM motif and participate in signaling to PI3 kinase (4).ErbB3 is highly expressed in many cancer cells (5) and activation of the ErbB3/PI3 kinase pathway is correlated with malignant phenotypes of adenocarcinomas (6). In tumor development, ErbB3 may function as an oncogenic unit together with other ErbB members, e.g. ErbB2 requires ErbB3 to drive breast tumor cell proliferation (7). Thus, prevention of the interaction between ErbB3 and ErbB tyrosine kinases has become a novel anti-tumor strategy.

  1. Yarden, Y. and Sliwkowski, M.X. (2001) Nature Rev. Mol. Cell. Biol. 2, 127-137.
  2. Guy, P.M. et al. (1994) Proc. Natl. Acad. Sci. USA 91, 8132-8136.
  3. Songyang, Z. et al. (1993) Cell 72, 767-778.
  4. Kim, H.H. et al. (1994) J. Biol. Chem. 269, 24747-24755.
  5. Sithanandam, G. et al. (2003) Carcinogenesis 24, 1581-1592.
  6. Kobayashi, M. et al. (2003) Oncogene 22, 1294-1301.
  7. Holbro, T. et al. (2003) Proc. Natl. Acad. Sci. USA 100, 8933-8938.

Application References

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This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.

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