Mechanism of erbB1 and erbB2 Hetero-Oligomerization
Abstract
We are developing an in vivo system using erbB/1L2 receptor chimerae in a B-cell line to investigate, the interactions and mechanism of oligomerization between the epidermal growth factor (EGF) receptor family members erbBl and erbB2. Since erbB2 overexpression has been strongly associated with breast cancer and has been shown to be a valuable target for breast cancer therapies, we are interested in dissecting its mechanism of activation. Heteromeric interaction between the intracellular domains of the 1L2 receptor beta and gamma chain will serve as a reporter for direct interaction between the extracellular domains of erbBl and erbB2 by mediating T or B-cell proliferation in the absence of 1L2. Previously, we have demonstrated erbBl homo-oligomerization and hetero-oligomerization with erbB2 in an EGF dependent manner. Due to problems in generating required cell lines expressing multiple chimeric receptors, we have not been able to address the remaining aims and have recently focused considerable effort to this end with little success. With further work, we hope to fully develop this assay to understand how erbBl and erbB2 interact and to provide insight into the mechanism by which erbB2 mediates transformation and tumorigenicity in cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA435261
Entities
People
- Jong W. Yu
- Mark A. Lemmon
Organizations
- University of Pennsylvania