Modeling Oscillations in the cAMP-PKA Network Within Budding Yeast

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2011

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Abstract

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.

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Gonzales, Kevin Edmond (2011). Modeling Oscillations in the cAMP-PKA Network Within Budding Yeast. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/5648.

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