Development of Strategies to Manipulate ErbB Receptor Heterodimerization from a Quantitative Analysis of Receptor/Ligand Relationships

摘要: Abstract : Members of the erbB family receptor tyrosine kinases include epidermal growth factor (EGF) and erbB2 (also known as HER-2/Neu) that is found overexpressed in many human breast cancer cases. The aim our studies to understand mechanism by which factors activate these receptors. If this can be understood detail, it should possible design approaches block inappropriate activation, occurs cancers. While EGF activates 1 (the receptor) directly inducing its homodimerization, same formation hetero-oligomeric complexes between erbB2. We have shown isolated extracellular domain sufficient for EGF-induced homodimerization receptor. By contrast, domains are not recapitulate hetero-oligomerization receptors has been observed vivo. These findings argue homo- occur though different mechanisms. Subsequently, using a variety analyzing transmodulation living cells, we generated data support homodimer-nucleated heterotetramer model. In case, an activated homodimer effective ligand erbB2, it. This view, although preliminary, provides new ideas developing reverse aberrant activation cancer.