THE QUANTITATIVE ANALYSIS OF TGF-β/SMAD SIGNALING DYNAMICS
Event details
| Date | 02.12.2009 |
| Hour | 14:00 |
| Speaker | Xuedong Liu, Associate Professor, University of Colorado-Boulder |
| Location |
SV1717a
|
| Category | Conferences - Seminars |
Cell responses to TGF-β signaling depend on the dynamics of Smad signaling and the interactions with many other signaling partners. Understanding TGF-β biology therefore requires studying the dynamics of the TGF-β/Smad signaling module in the context of its integration in the cellular signaling network, which is a task well suited to mathematical and computational modeling. We developed a mathematical model of canonical Smad signaling based on published data and our experimentally determined cellular Smad concentrations as well as Smad phosphorylation kinetics. Our modeling analysis implicates that changes in TGF-ß exposure can alter Smad signaling amplitude and duration. Through a systematic quantitative and experimental analysis of how TGF-β ligand concentration is transduced into downstream phospho-Smad2 kinetics, we demonstrated that the rate of TGF-β ligand depletion is the principal determinant of the Smad signal duration. TGF-β depletion is caused by two mechanisms: 1) cellular uptake of TGF-β by a TGF-β type II receptor-dependent mechanism and 2) reversible binding of TGF-β to the cell surface. Our results indicate that cells sense TGF-β dose by depleting TGF-β via constitutive TGF-β type II receptor trafficking processes. We discovered that TGF-β signaling dynamics can be altered by the viral oncoprotein v-ErbA. The mechanism by which v-ErbA perturbs TGF-β signaling will also be discussed.
Practical information
- General public
- Free
Contact
- Anne-Marie Rodel