title: Modeling and stochastic simulation of the Ras/cAMP/PKA pathway in the yeast Saccharomyces cerevisiae evidences a key regulatory function for intracellular guanine nucleotides pools.
abstract: In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway is involved in the regulation of metabolism and cell cycle progression. The pathway is tightly regulated by several control mechanisms, as the feedback cycle ruled by the activity of phosphodiesterase. Here, we present a discrete mathematical model for the Ras/cAMP/PKA pathway that considers its principal cytoplasmic components and their mutual interactions. The tau-leaping algorithm is then used to perform stochastic simulations of the model. We investigate this system under various conditions, and we test how different values of several stochastic reaction constants affect the pathway behaviour. Finally, we show that the level of guanine nucleotides, GTP and GDP, could be relevant metabolic signals for the regulation of the whole pathway.
authors.affiliation: Università degli Studi di Milano-Bicocca, Dipartimento di Informatica, Sistemistica e Comunicazione, Viale Sarca 336, 20126 Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cazzaniga
authors.forename: Dario
authors.initials: D
authors.lastname: Pescini
authors.forename: Daniela
authors.initials: D
authors.lastname: Besozzi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Mauri
authors.forename: Sonia
authors.initials: S
authors.lastname: Colombo
authors.forename: Enzo
authors.initials: E
authors.lastname: Martegani
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000378:metabolism; D025461:Feedback, Physiological; D018628:Gene Dosage; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D013269:Stochastic Processes; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D006150:Guanine Nucleotides; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D018631:ras Proteins