%0 Journal Article
%T The role of feedback control mechanisms on the establishment of oscillatory regimes in the Ras/cAMP/PKA pathway in S. cerevisiae
%A Daniela Besozzi
%A Paolo Cazzaniga
%A Dario Pescini
%A Giancarlo Mauri
%A Sonia Colombo
%A Enzo Martegani
%J EURASIP Journal on Bioinformatics and Systems Biology
%D 2012
%I BioMed Central
%R 10.1186/1687-4153-2012-10
%X In living cells many processes are regulated by negative and positive feedback mechanisms, which are usually interlaced in complex regulatory networks and can function to either attenuate, amplify or even exploit molecular noise and stochasticity (see, e.g., [1-3] and references therein). As a matter of fact, molecular fluctuations do not always represent a negative feature for the proper functioning of a cellular system, on the contrary they can be advantageous to widen the range of stimulus-response to different perturbations, therefore promoting the adaptability to changeable environments. In this context, computational models represent an indispensable tool to investigate the complexity of the systems where multiple feedback and feedforward loops occur, multiple feedback and feedforward loops, as well as to reveal their emergent behaviors, as the use of experimental analysis alone is typically not able to unravel the whole picture of these (inhibitory or activatory) molecular interactions cascade [4-6].A signal transduction pathway that is characterized by such complexity is the Ras/cAMP/PKA pathway in the yeast Saccharomyces cerevisiae, which regulates metabolism and cell cycle progression in response to nutritional sensing and stress conditions [7-10]. In budding yeast, five interlocked systems are known to participate in glucose signaling, which altogether result in a massive restructuring of the transcriptional state of the genome, as well as in a rapid change in the pattern of protein phosphorylation when glucose is added to cells growing on a non-fermentable carbon source [11]. Among these five pathways, the Ras/cAMP/PKA system plays a central role in responding to changes in glucose concentration and in turning on the processes that lead to cellular growth and division.In particular, the Ras/cAMP/PKA pathway controls more than 90% of all genes that are regulated by glucose through the activation of the protein kinase A (PKA), that is able to phosphorylate
%U http://bsb.eurasipjournals.com/content/2012/1/10