BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:THE QUANTITATIVE ANALYSIS OF TGF-β\;/SMAD SIGNALING DYNAMICS DTSTART:20091202T140000 DTSTAMP:20260428T041007Z UID:fa20abc73ed24aa8b481bae787709e75106e65eb9e76eed9c5250d74 CATEGORIES:Conferences - Seminars DESCRIPTION:Xuedong Liu\, Associate Professor\, University of Colorado-Bou lder\nCell responses to TGF-β signaling depend on the dynamics of Smad si gnaling and the interactions with many other signaling partners. Understan ding TGF-β biology therefore requires studying the dynamics of the TGF-β /Smad signaling module in the context of its integration in the cellular s ignaling network\, which is a task well suited to mathematical and computa tional modeling. We developed a mathematical model of canonical Smad sign aling based on published data and our experimentally determined cellular S mad concentrations as well as Smad phosphorylation kinetics. Our modeling analysis implicates that changes in TGF-ß exposure can alter Smad signal ing amplitude and duration. Through a systematic quantitative and experim ental analysis of how TGF-β ligand concentration is transduced into downs tream phospho-Smad2 kinetics\, we demonstrated that the rate of TGF-β lig and depletion is the principal determinant of the Smad signal duration. TG F-β depletion is caused by two mechanisms: 1) cellular uptake of TGF-β b y 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 traff icking processes. We discovered that TGF-β signaling dynamics can be alt ered by the viral oncoprotein v-ErbA. The mechanism by which v-ErbA pertu rbs TGF-β signaling will also be discussed. LOCATION:SV1717a STATUS:CONFIRMED END:VEVENT END:VCALENDAR