Characterizing SHP2 as a Novel Therapeutic Target in Breast Cancer
Abstract
Over the course of the past year, our purpose has been to identify important binding components that contribute to Shp2 substrate selectivity in an effort to contribute knowledge toward designing a selective Shp2 inhibitor. We have confirmed that the peptide based on a Shp2 substrate inhibits Shp2 and not the close homologue Shp1. Molecular modeling shows that point mutations at acidic residue do not always confer defects in binding. Results suggest that the -1 and -4 position acidic residues are critical for binding. A surprising finding from the modeling showed that the -2 acidic amino acid inhibited interactions of the peptide with the active site of Shp2. The knowledge that we gleaned from these studies was used to predict and characterize a substrate for Shp2, focal adhesion kinase. We intend to utilize this knowledge as we move forward in studying Shp2 action on HER2 through mutagenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2012
- Accession Number
- ADA560203
Entities
People
- Zachary C Hartman
Organizations
- West Virginia University