EphA2 Kinase Agonists as Novel Suppressors of Both Prostate Cancer Cell Motility and Growth Structure
Abstract
Cancer metastasis involves tumor cell dissemination to and uncontrolled growth at distal organs. Research in this lab shows that activation of endogenous EphA2 kinase in prostate cancer cell lines suppressed cell proliferation by targeting Ras/MAPK pathway and inhibited integrin-mediated cell migration. The goal of the proposal is to develop novel EphA2 agonists and to test their effects on prostate cancer progression. Toward this goal, we proposed to solve the crystal structure of EphA2 kinase in complex with the native ligand as well as a small peptide that we have isolated from phage display library. In addition, we planned to investigate the molecular mechanisms behind the suppressive effects of EphA2 on Ras/MAPK pathway. Much progress has been made during the past year. A new method has been developed to purify EphA2 ligand binding domain and ephrin-Al ectodomain, which are being used in structural studies. New in vivo model systems have adapted for in vivo testing of new EphA2 agonists. The potential involvement of candidate signaling and adaptor proteins in the suppression of Ras/MAPK pathway has been examined. The results complement those from domain swapping and mutagenesis studies, and suggest that novel signaling pathways are initiated from the activated EphA2 kinase.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410229
Entities
People
- Bingcheng Wang
Organizations
- Case Western Reserve University