Modeling Oscillations in the cAMP-PKA Network Within Budding Yeast
In our work we develop and analyze an ordinary differential equation
model that describes the cyclic adenosine monophosphate (cAMP) --Protein Kinase A (PKA) pathway in budding yeast. In particular our
model describes the effect of glucose stimulation on the concentration of cAMP in the short term,
and the effect of stress in the long term. We develop this model in
order to understand two specific experimental results, reported by
Ma et al. (1999) and Garmendia-Torres et al. (2007). In order to describe the
surprising results published by Ma et al. (1999) we make a key assumption
that three enzymes within the cAMP-PKA network compete with one
another for activation by PKA. This assumption sets our model apart
from previous models of the cAMP-PKA network.
Our model focuses on two forms of negative feedback that
drive oscillations in the concentration of cAMP. Under high or low
stress conditions (for example, following glucose stimulation) our model reduces to a single negative
feedback loop, resulting in decaying oscillations in the concentration of cAMP towards a unique
equilibrium point. Under intermediate stress levels, a second negative feedback loop also exists, resulting in the possible loss of stability
through a Hopf bifurcation, which leads to sustained oscillations in the concentration of cAMP. Given the novel prediction that
the concentration of cAMP experiences decaying oscillations for a
wide range of parameters, our collaborators in biology, Dr. Magwene's Lab, undertook new experiments in
which they verified decaying cAMP oscillations at low stress levels. In an initial
experiment they also verify the possibility of sustained oscillations at intermediate stress levels as predicted by our model.
Our model of the cAMP-PKA network has both predictive and explanatory
power and will serve as a foundation for future mathematical and
experimental studies of this key signaling network.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.
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