The Role of TSC2 Phosphorylation in the Regulation of TSC2 Localization and mTOR Signaling
Abstract
Tuberous sclerosis is a genetic disease that affects an estimated 1 in 6,000 births, and it occurs when mutations in components of the tuberous sclerosis complex (TSC) render it functionally inactive. Research over the last decade has established that the TSC controls the activity of a signaling molecule called mTOR, and aberrant regulation of the TSC/mTOR pathway has become widely implicated in the pathogenesis of tuberous sclerosis. However, the mechanism(s) through which the TSC regulates mTOR signaling have not been resolved. Our overall hypothesis predicts that agonists, such as mechanical signals, regulate mTOR signaling by inducing a phosphorylation-dependent loss in the association of TSC2 with late endosomal / lysosomal system. During the first year of this project we have successfully identified 6 phosphorylation sites on TSC2 that are regulated by mechanical stimuli. We then generated phosphodefective mutants of TSC2 and our preliminary results with these mutants indicate that these phosphorylation sites play a central role in the pathway through which mechanical stimuli regulate mTOR signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2015
- Accession Number
- ADA620353
Entities
People
- Troy A. Hornberger
Organizations
- University of Wisconsin–Madison