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

Cazzaniga, Paolo; Pescini, Dario; Besozzi, Daniela; Mauri, Giancarlo; Colombo, Sonia; Martegani, Enzo

doi:10.1016/j.jbiotec.2007.09.019

Cited by 42 publications

(53 citation statements)

References 33 publications

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“…The mechanism by which glucose phosphorylation affects Ras-GTP loading remains largely to be elucidated. It is known that Cdc25 is required for the glucose-induced Ras-GTP increase and it was suggested that the intracellular levels of GTP, which quickly respond to nutrient availability, could be the metabolic signal that regulates Cdc25 activity in response to glucose (Rudoni et al 2001;Colombo et al 2004;Cazzaniga et al 2008). On the other hand, it seems plausible that the Ira proteins are inhibited by the glucose signal, since an ira1Dira2D double deletion mutant displays a severe increase in Ras-GTP levels and no further increase upon glucose addition (Colombo et al 2004).…”

Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 99%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

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Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 99%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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“…In contrast to prior work (Garmendia-Torres et al ., 2007; Cazzaniga et al ., 2008), we did not seek to build a model that reflects all known biochemical interactions surrounding PKA signaling. Instead, by capturing only the known essential interactions in the PKA system, we aimed to build a simple model that could recapitulate the pulse of Msn2 translocation after a bPAC pulse.…”

Section: Resultsmentioning

confidence: 99%

Model-guided optogenetic study of PKA signaling in budding yeast

Stewart-Ornstein

Chen

Bhatnagar

et al. 2017

MBoC

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“…At Ø = 0, we simulate a step increase in the cytoplasm of the concentration of one of the species to 0 14 ÑÅ (4 2 ¡ 10 6 molecules) while the other has a concentration of 10 Å (3 ¡ 10 5 molecules). These numbers correspond roughly to the copy numbers of GTP and cAMP used in the model from (10). In this test scenario, neither of the small species interact with the proteins in the cytosolic and nuclear module but they diffuse with = 250 Ñ 2 × making the model stiff.…”

Section: Scenario 2: Two Small Species Inside the Cellmentioning

confidence: 88%

“…One recent example with small molecules is a well stirred stochastic model of the Ras/cAMP/PKA pathway with explicit modeling of ATP, GTP, GDP and cAMP (10). These smaller molecules are, at least in some time intervals, present in many copies and they are diffusing rapidly compared to less abundant, larger proteins.…”

Section: Scenario 2: Two Small Species Inside the Cellmentioning

confidence: 99%

An adaptive algorithm for simulation of stochastic reaction–diffusion processes

Ferm

Hellander

Lötstedt

2010

Journal of Computational Physics

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We propose an adaptive hybrid method suitable for stochastic simulation of diffusion dominated reaction-diffusion processes. For such systems, simulation of the diffusion requires the predominant part of the computing time. In order to reduce the computational work, the diffusion in parts of the domain is treated macroscopically, in other parts with the tau-leap method and in the remaining parts with Gillespie's stochastic simulation algorithm (SSA) as implemented in the next subvolume method (NSM). The chemical reactions are handled by SSA everywhere in the computational domain. A trajectory of the process is advanced in time by an operator splitting technique and the time steps are chosen adaptively. The spatial adaptation is based on estimates of the errors in the tau-leap method and the macroscopic diffusion. The accuracy and efficiency of the method are demonstrated in examples from molecular biology where the domain is discretized by unstructured meshes.

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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

Cited by 42 publications

References 33 publications

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Model-guided optogenetic study of PKA signaling in budding yeast

An adaptive algorithm for simulation of stochastic reaction–diffusion processes

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