Functional Sites of the erbB-2 Receptor and Its Activator Heregulin
Abstract
Aberrant expression of the erbB-2 (HER-2/neu) receptor occurs in up to 30% of human breast cancers and correlates with aggressive disease and poor prognosis. The growth factor heregulin (HRG) binds to erbB-3 or erbB-4, promoting heterodimerization with erbB-2, inducing autophosphorylation and activation of erbB-2 signaling. It is generally accepted that HRG and erbB-2 do not interact directly. Depending on its concentration HRG can either inhibit or stimulate cell proliferation in cell lines that overexpress erbB-2. This suggests some type of direct interaction between HRG and erbB-2. Solution structure of HRG and other data support the existence of a low affinity-binding site within the EGF-like domain of HRG. The goal of the proposed experiments is to define the predicted sites of interaction between HRG and the erbB-2 receptor through generation of HRG and erbB-2 deletion mutants. During the first year of funding, I maintained the timeline outlined in the statement of work: a) generated deletions mutants of ErbB-2 lacking the putative heregulin binding site or site important for receptor heterodimerization and b) initiated the construction of heregulin mutants. The main result of my work was generating 8 deletions of the ErbB-2 extracellular domain. These mutants will be used in the experiments determining the mechanism of interaction between ErbB-2 and heregulin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385237
Entities
People
- Joanna Mroczkowska-jasiska
Organizations
- University of California, Berkeley