p185 super(HER2) signal transduction in breast cancer cells

A partially agonistic monoclonal antibody, 4D5, known to bind to the extracellular domain of p185 super(HER2) and shown to inhibit long term growth of p185 super(HER2) overexpressing breast cancer cells, was used to study signal transduction and phosphotyrosyl protein substrates associated with this receptor. The results indicate that short term (< 6 h) 4D5 activation of p185 super(HER2) in overexpressing breast cancer cells produces agonistic-like signaling typical of homologous tyrosine kinase growth factor receptors such as epidermal growth factor receptor. The data also suggest that ptyr56 represents a novel phosphorylated substrate associated with 4D5-stimulated p185 super(HER2).