Determine the Mechanism by which Specific ERbB Receptor Dimers Differ in Their Ability to Disrupt Epithelial Cell Polarity
Abstract
ErbB2 is overexpressed in approximately 25% of breast cancers. ErbB2 homodimers can cause an increase in cell proliferation and a disruption of cell polarity, both characteristics of early cancer stages. In order to dissect the role of ErbB2 biochemistry on cell polarity we have constructed two series of mutations in the autophosphorylation sites of chimeric Neu (rat ErbB2). The chimeric receptor is used in order to create an inducible system of Neu homodimers. In one series 4 of the 5 autophosphorylated tyrosines are active. In the other only one of these tyrosines is active (Y mutants). Preliminary results suggest that different Y mutations can cause distinct cell polarity disruption phenotypes. More in depth studies of these phenotypes are planned for the near future, including some preliminary studies to look at possible changes in the three major polarity complexes - Par, Crumbs and Lgl. In order to investigate the role localization plays in ErbB2's ability to promote proliferation and disrupt polarity, we have also constructed a series of mutations that cause mislocalization of chimeric ErbB2. Preliminary data suggests that ErbB2 cannot phosphorylate from the apical surface, but must be located on the lateral surface-where wild type ErbB2 normally localizes - or in a non-polarized cell. After more in depth testing of this hypothesis, we shall attempt to find the factor(s) responsible for the inability of ErbB2 to phosphorylate from the apical surface.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425954
Entities
People
- Alexandra V. Luca
Organizations
- Cold Spring Harbor Laboratory