Role of NF1 and NF2 in Signaling and Transformation
Abstract
Our studies have concentrated on the mechanism by which NF2 may function as a tumor suppressor. We determined that NF2 blocks Ras transformation, in part, by blocking the action of the Rac small GTPase. We then focused our efforts on further assessing the mechanism by which NF2 antagonizes Rac signaling and function. Progress has been made in two main directions. We determined that NF2 can block multiple Rac-mediated signaling activities. This suggests that NF2 inhibition of Rac function is not due to inhibition of a subset of Rac signaling events and argues that NF2 may directly modulate Rac itself. This outcome was an unexpected. Based on an observation by our collaborators, Rac was found to cause phosphorylation of NF2. The consequences of this phosphorylation on NF2 negative modulation of Rac transforming activity was determined. When taken together, these observations may provide a key clue regarding the tumor suppressing function of NF2. Rac function has been found to be necessary for the transforming actions of Ras and other oncoproteins. Therefore, if NF2 is a negative modulator of Rac function, it may serve as a negative modulator of growth regulation by a spectrum of growth promoting signaling proteins. -__ ____________
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA407273
Entities
People
- Channing Der
Organizations
- University of North Carolina at Chapel Hill