Search for Physiological Substrates of Protein Tyrosine Phosphatase Epsilon in Mammary Tumor Cell Lines
Abstract
Previous studies have established a connection between overexpression of the receptor- type tyrosine phosphatase Epsilon (PTPe) and mammary tumors induced in mice by the Neu oncogene. This project aimed to understand the role of PTPe in mammary tumorigenesis by identification of physiological substrates of PTPe and by understanding the effect of PTPe on their function. In the course of these studies we constructed several substrate- trapping mutants of PTPe, which can bind to and help isolate PTPe substrates. Trapping mutants showed, and additional biochemical and cellular studies confirmed, that the delayed-rectifier, voltage-gated potassium channels Kvl.5 and Kv2.l, as well as the Src tyrosine kinase, are physiological substrates of PTPe. Examination of PTPe-deficient mice revealed that lack of PTPe correlated with hyperphosphorylation and activation of Kvl.5 and K2.l, as well as with severe transient hypomyelination of sciatic nerves of young post-natal mice. Mammary tumors induced by Neu in PTPe-deficient mice exhibited altered Src phosphorylation and activity and grew poorly in culture and in vivo. These and other experiments outlined here indicate that PTPe is a physiological inactivator of Kv channels and a physiological activator of Src in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2001
- Accession Number
- ADB282187
Entities
People
- Ari Elson
Organizations
- Weizmann Institute of Science