HER/ErbB Family Antibody Sampler Kit #8339
Product Information
Kit Usage Information
Protocols
- 2243: Western Blotting, Immunohistochemistry (Paraffin)
- 2842: Western Blotting, Immunoprecipitation (Magnetic), Immunohistochemistry (Paraffin)
- 3777: Western Blotting, Fluorescent Western, Immunohistochemistry (Paraffin), Immunofluorescence, Flow
- 4267: Western Blotting, Immunoprecipitation (Agarose), Immunohistochemistry (Leica® Bond™), Immunohistochemistry (Paraffin), Immunofluorescence, Flow
- 4290: Western Blotting, Immunohistochemistry (Leica® Bond™), Immunohistochemistry (Paraffin)
- 4757: Western Blotting
- 4795: Western Blotting, Immunoprecipitation (Magnetic)
- 7074: Western Blotting
- 12708: Western Blotting, Immunoprecipitation (Agarose), Immunohistochemistry (Leica® Bond™), Immunohistochemistry (Paraffin), Immunofluorescence, Flow
Product Description
Specificity / Sensitivity
Source / Purification
Background
The ErbB2 (HER2) proto-oncogene encodes a 185 kDa transmembrane, receptor-like glycoprotein with intrinsic tyrosine kinase activity (4). 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 (5). Amplification of the ErbB2 gene and overexpression of its product are detected in almost 40% of human breast cancers (6). 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 (4,7).
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 (8,9). 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 (10). Both Tyr1222 and Tyr1289 of ErbB3 reside within a YXXM motif and participate in signaling to PI3 kinase (11).
HER4/ErbB4, like other family members, has four ectodomains, a single transmembrane domain, and a cytoplasmic tail containing the active tyrosine kinase domain (12). By binding to neuregulins and/or EGF family ligands, ErbB4 forms either a homodimer or heterodimer with other ErbB family members, which results in receptor activation and signaling (12). ErbB4 is ubiquitously expressed with the highest expression occurring in the brain and heart. The expression of ErbB4 in breast cancer, pediatric brain cancer, and other types of carcinomas has been reported, suggesting that ErbB4 expression is involved in both normal tissue development and carcinogenesis (12).
- Hackel, P.O. et al. (1999) Curr Opin Cell Biol 11, 184-9.
- Zwick, E. et al. (1999) Trends Pharmacol Sci 20, 408-12.
- Rojas, M. et al. (1996) J Biol Chem 271, 27456-61.
- Muthuswamy, S.K. et al. (1999) Mol Cell Biol 19, 6845-57.
- Qian, X. et al. (1994) Proc Natl Acad Sci U S A 91, 1500-4.
- Dittadi, R. and Gion, M. (2000) J Natl Cancer Inst 92, 1443-4.
- Kwon, Y.K. et al. (1997) J Neurosci 17, 8293-9.
- Yarden, Y. and Sliwkowski, M.X. (2001) Nat Rev Mol Cell Biol 2, 127-37.
- Guy, P.M. et al. (1994) Proc Natl Acad Sci U S A 91, 8132-6.
- Songyang, Z. et al. (1993) Cell 72, 767-78.
- Kim, H.H. et al. (1994) J Biol Chem 269, 24747-55.
- Carpenter, G. (2003) Exp Cell Res 284, 66-77.
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