ErbB2 Regulation of c-src Activity in Breast Cancer
Abstract
Previous results (Year 1) indicated that human breast epithelial cells transfected with ErbB2 exhibited increased activity, but not expression, of c-src. This increase was associated with decreased phosphorylation on tyrosine 527. In year 2, the expression and activity of C-terminal src kinase (CSK), responsible for phosphorylating src on Y527 was found to be increased by ErbB2. However, an even greater increase in activity of phosphatases directed toward the C-terminus of src was observed. This phosphatase was found to physically associate with ErbB2, and has been tentatively identified as SHP2. This suggests that ErbB2 physically associates with and activates SHP2, which removes an inhibitory phosphate at position 527 in src. Preliminary results using inhibitor src constructs indicate that src activation by ErbB2 may be important in mediating some aspects of tumor progression. In particular, the ability of cells to grow on soft agar was inhibited by inhibition of src activation. These results suggest that src, or the kinases and phosphatases regulating src, may provide useful targets for breast cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA359205
Entities
People
- Lewis G. Sheffield
Organizations
- University of Wisconsin–Madison