Kformula

TGFbeta Signalling Feedback Loops


Transforming growth factor β (TGF-β) ligands activate a signaling cascade with multiple cell context dependent outcomes. Disruption or disturbance leads to variant clinical disorders. To develop strategies for disease intervention, delineation of the pathway in further detail is required. Current theoretical models of this pathway describe production and degradation of signal mediating proteins and signal transduction from the cell surface into the nucleus, whereas feedback loops have not exhaustively been included.
In this study we present a mathematical model to determine the relevance of feedback regulators (Arkadia, Smad7, Smurf1, Smurf2, SnoN and Ski) on TGF-β target gene expression and the potential to initiate stable oscillations within a realistic parameter space. We employed massive sampling of the parameters space to pinpoint crucial players for potential oscillations as well as transcriptional product levels. We identified Smad7 and Smurf2 with the highest impact on the dynamics. Based on these findings, we conducted preliminary time course experiments.

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Filename Format Size Action
BIOMD0000000410.xml XML document 216 KB Download

Organism: Mus musculus

Model type: Ordinary differential equations (ODE)

Model format: SBML

Execution or visualisation environment: Copasi

Model image: (Click on the image to zoom)

help Contributors

[Anastasia Bachmann] [Philippe Lucarelli] [Sven Sahle] [Christoph Meyer] [Ursula Klingmüller]
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help Other Contributors

Katja Wegner, Jan-Ulrich Schad, Peter Nickel

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None

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Views: 1704    Downloads: 821
  • Created: 5th Feb 2013 at 18:28
  • Last updated: 5th Feb 2013 at 18:33
  • Last used: 16th Dec 2017 at 00:18

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