ArticleBMC systems biology2009
Deterministic mathematical models of the cAMP pathway in Saccharomyces cerevisiae.
Article in BMC systems biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 25 citations in OpenAlex.
- A two-dimensional finite element model of intercellular cAMP signaling through gap junction channels.Journal of biomechanics · 2023Article
- Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway.iScience · 2023Article
- A mathematical model captures the role of adenyl cyclase Cyr1 and guanidine exchange factor Ira2 in creating a growth-to-hyphal bistable switch in Candida albicans.FEBS open bio · 2022Article
- Modeling and analysis of the macronutrient signaling network in budding yeast.Molecular biology of the cell · 2021Article
- Article
- A two-dimensional finite element model of cyclic adenosine monophosphate (cAMP) intracellular signaling.SN applied sciences · 2019Article
- Using Systems Biology and Mathematical Modeling Approaches in the Discovery of Therapeutic Targets for Spinal Muscular Atrophy.Advances in neurobiology · 2018Review
- Complex regulation of Hsf1-Skn7 activities by the catalytic subunits of PKA in Saccharomyces cerevisiae: experimental and computational evidences.BMC systems biology · 2015Article
- Systems biology investigation of cAMP modulation to increase SMN levels for the treatment of spinal muscular atrophy.PloS one · 2014Article
- Modeling mutant phenotypes and oscillatory dynamics in the Saccharomyces cerevisiae cAMP-PKA pathway.BMC systems biology · 2013Article
- Effect of regulatory architecture on broad versus narrow sense heritability.PLoS computational biology · 2013Article
- Nutritional control of growth and development in yeast.Genetics · 2012Review
- Toward a multiscale description of microvascular flow regulation: o(2)-dependent release of ATP from human erythrocytes and the distribution of ATP in capillary networks.Frontiers in physiology · 2012Article
- Structurally robust biological networks.BMC systems biology · 2011Article
- Ras signaling in yeast.Genes & cancer · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCyclic adenosine monophosphate (cAMP) has a key signaling role in all eukaryotic organisms. In Saccharomyces cerevisiae, it is the second messenger in the Ras/PKA pathway which regulates nutrient sensing, stress responses, growth, cell cycle progression, morphogenesis, and cell wall biosynthesis. A stochastic model of the pathway has been reported.
resultsWe have created deterministic mathematical models of the PKA module of the pathway, as well as the complete cAMP pathway. First, a simplified conceptual model was created which reproduced the dynamics of changes in cAMP levels in response to glucose addition in wild-type as well as cAMP phosphodiesterase deletion mutants. This model was used to investigate the role of the regulatory Krh proteins that had not been included previously. The Krh-containing conceptual model reproduced very well the experimental evidence supporting the role of Krh as a direct inhibitor of PKA. These results were used to develop the Complete cAMP Model. Upon simulation it illustrated several important features of the yeast cAMP pathway: Pde1p is more important than is Pde2p for controlling the cAMP levels following glucose pulses; the proportion of active PKA is not directly proportional to the cAMP level, allowing PKA to exert negative feedback; negative feedback mechanisms include activating Pde1p and deactivating Ras2 via phosphorylation of Cdc25. The Complete cAMP model is easier to simulate, and although significantly simpler than the existing stochastic one, it recreates cAMP levels and patterns of changes in cAMP levels observed experimentally in vivo in response to glucose addition in wild-type as well as representative mutant strains such as pde1Delta, pde2Delta, cyr1Delta, and others. The complete model is made available in SBML format.
conclusionWe suggest that the lower number of reactions and parameters makes these models suitable for integrating them with models of metabolism or of the cell cycle in S. cerevisiae. Similar models could be also useful for studies in the human pathogen Candida albicans as well as other less well-characterized fungal species.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.