ArticleBiophysical journal2006
Bistability, stochasticity, and oscillations in the mitogen-activated protein kinase cascade.
Article in Biophysical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- EMBED: Ensemble MATCONT-Based Detection and Classification of Bifurcations in Dual Phosphorylation-Dephosphorylation Reaction Networks.ACS omega · 2026Article
- CellDynaMo-stochastic reaction-diffusion-dynamics model: Application to search-and-capture process of mitotic spindle assembly.PLoS computational biology · 2022Article
- IDH2-mediated regulation of the biogenesis of the oxidative phosphorylation system.Science advances · 2022Article
- Quantitative analysis of the yeast pheromone pathway.Yeast (Chichester, England) · 2019Article
- Mitogen-activated protein kinase (MAPK) dynamics determine cell fate in the yeast mating response.The Journal of biological chemistry · 2017Article
- Article
- Including Rebinding Reactions in Well-Mixed Models of Distributive Biochemical Reactions.Biophysical journal · 2016Article
- Spatio-temporal dynamics of a cell signal pathway with negative feedbacks: the MAPK/ERK pathway.The European physical journal. E, Soft matter · 2016Article
- ACCURATE CHEMICAL MASTER EQUATION SOLUTION USING MULTI-FINITE BUFFERS.Multiscale modeling & simulation : a SIAM interdisciplinary journal · 2016Article
- Article
- Stochastic simulation of Boolean rxncon models: towards quantitative analysis of large signaling networks.BMC systems biology · 2015Article
- Spatial stochastic dynamics enable robust cell polarization.PLoS computational biology · 2013Article
- Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificity.Molecular biology of the cell · 2012Article
- Factorized time-dependent distributions for certain multiclass queueing networks and an application to enzymatic processing networks.Queueing systems · 2011Article
- Trafficking motifs as the basis for two-compartment signaling systems to form multiple stable states.Biophysical journal · 2011Article
- Synthesis of robust tunable oscillators using mitogen activated protein kinase cascades.Systems and synthetic biology · 2010Article
- Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.PLoS biology · 2010Article
- The effects of replacing Sst2 with the heterologous RGS4 on polarization and mating in yeast.Biophysical journal · 2010Article
- Signalling ballet in space and time.Nature reviews. Molecular cell biology · 2010Review
- Cell cycle-dependent variations in protein concentration.Nucleic acids research · 2010Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Signaling pathways respond to stimuli in a variety of ways, depending on the magnitude of the input and the physiological status of the cell. For instance, yeast can respond to pheromone stimulation in either a binary or graded fashion. Here we present single cell transcription data indicating that a transient binary response in which all cells eventually become activated is typical. Stochastic modeling of the biochemical steps that regulate activation of the mitogen-activated protein kinase Fus3 reveals that this portion of the pathway can account for the graded-to-binary conversion. To test the validity of the model, genetic approaches are used to alter expression levels of Msg5 and Ste7, two of the proteins that negatively and positively regulate Fus3, respectively. Single cell measurements of the genetically altered cells are shown to be consistent with predictions of the model. Finally, computational modeling is used to investigate the effects of protein turnover on the response of the pathway. We demonstrate that the inclusion of protein turnover can lead to sustained oscillations of protein concentrations in the absence of feedback regulation. Thus, protein turnover can profoundly influence the output of a signaling pathway.
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