Mechanistic model of the Ras/cAMP/PKA in yeast S.cerevisiae. The Ras/cAMP/PKA pathway plays a major role in the regulation of metabolism, stress resistance and cell cycle progress and is tightly regulated by multiple feedback loops, exerted by the protein kinase A (PKA). This model investigates the dynamics of the second messenger cAMP on Ras/cAMP/PKA pathway, to determine the effects of the feedback mechanisms on establising stable oscillatory regimes.
The model has been defined according to the stochastic formulation of chemical kinetics [Gillespie DT, 1977] , which requires to specify the set of molecular species occurring in the pathway and their respective interactions, formally described as a set of biochemical reactions.
The volume considered for this system is 30fL; this value can be used to convert the model into the deterministic formulation.
This model is described in the article:
Abstract:
In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway is involved in the regulation of cell growth and proliferation in response to nutritional sensing and stress conditions. The pathway is tightly regulated by multiple feedback loops, exerted by the protein kinase A (PKA) on a few pivotal components of the pathway. In this article, we investigate the dynamics of the second messenger cAMP by performing stochastic simulations and parameter sweep analysis of a mechanistic model of the Ras/cAMP/PKA pathway, to determine the effects that the modulation of these feedback mechanisms has on the establishment of stable oscillatory regimes. In particular, we start by studying the role of phosphodiesterases, the enzymes that catalyze the degradation of cAMP, which represent the major negative feedback in this pathway. Then, we show the results on cAMP oscillations when perturbing the amount of protein Cdc25 coupled with the alteration of the intracellular ratio of the guanine nucleotides (GTP/GDP), which are known to regulate the switch of the GTPase Ras protein. This multi-level regulation of the amplitude and frequency of oscillations in the Ras/cAMP/PKA pathway might act as a fine tuning mechanism for the downstream targets of PKA, as also recently evidenced by some experimental investigations on the nucleocytoplasmic shuttling of the transcription factor Msn2 in yeast cells.
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The role of feedback control mechanisms on the establishment of oscillatory regimes in the Ras/cAMP/PKA pathway in S. cerevisiae.
- Daniela Besozzi, Paolo Cazzaniga, Dario Pescini, Giancarlo Mauri, Sonia Colombo, Enzo Martegani
- EURASIP journal on bioinformatics & systems biology , 7/ 2012 , Volume 2012 , Issue 1 , pages: 10 , PubMed ID: 22818197
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Paolo Cazzaniga
Metadata information
isDescribedBy (1 statement)
isDerivedFrom (2 statements)
hasTaxon (1 statement)
hasPart (3 statements)
Gene Ontology cAMP-mediated signaling
Pathway Ontology protein kinase A (PKA) signaling pathway
hasProperty (1 statement)
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