Regulation of the Tumor Suppressor Protein PTEN by Phosphorylation
Abstract
The purpose of the research project of this grant is to study the role of phosphorylation on the regulation of PTEN, a tumor suppressor localized on a chromosome region frequently deleted in various cancers including prostate cancer. Preliminary data presented in the research proposal indicated that PTEN is a phosphoprotein. I mapped the major phosphorylation sites of PTEN to the C-terminus domain (the tail). I generated phospho-specific antibodies and used them to determine that phosphorylation of the Tail is not sensitive to growth factors, confluency or adhesion. I also demonstrated that the phosphorylation of the PTEN tail regulates its protein stability and its activity. Interestingly, I have also found that phosphorylated PTEN exits in a more closed' conformation and is unable to interact with MAGI-2. However, unphosphorylated PTEN strongly interacts with MAGI-2 to regulate Akt. This results made us propose a model in which PTEN can be found in two different states. If the Tail is phosphorylated PTEN is in a closed' conformation free in the cytoplasm. When unphosphorylated PTEN can bind to PDZ containing proteins and be recruited to the plasma membrane where can perform its function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398955
Entities
People
- Fancisca Vasquez
Organizations
- Dana–Farber Cancer Institute