ArticleMolecular biology of the cell2016
Long-term dynamics of multisite phosphorylation.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Mathematical Modeling for Oscillations Driven by Noncoding RNAs.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Widespread biochemical reaction networks enable Turing patterns without imposed feedback.Nature communications · 2024Article
- Bifunctional enzyme provides absolute concentration robustness in multisite covalent modification networks.Journal of mathematical biology · 2024Article
- Article
- Topological descriptors of the parameter region of multistationarity: Deciding upon connectivity.PLoS computational biology · 2023Article
- Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression.Nucleic acids research · 2022Article
- Identification, visualization, statistical analysis and mathematical modeling of high-feedback loops in gene regulatory networks.BMC bioinformatics · 2021Article
- Symmetry breaking meets multisite modification.eLife · 2021Article
- Dynamics of ERK regulation in the processive limit.Journal of mathematical biology · 2021Article
- Exploring cyclic networks of multisite modification reveals origins of information processing characteristics.Scientific reports · 2020Article
- Robustness and parameter geography in post-translational modification systems.PLoS computational biology · 2020Article
- Absolutely robust controllers for chemical reaction networks.Journal of the Royal Society, Interface · 2020Article
- Oscillations and bistability in a model of ERK regulation.Journal of mathematical biology · 2019Article
- When More Is Less: Dual Phosphorylation Protects Signaling Off State against Overexpression.Biophysical journal · 2018Article
- A quantitative model of developmental RTK signaling.Developmental biology · 2018Review
- Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling.Cell systems · 2018Article
- Exploring the intrinsic behaviour of multisite phosphorylation systems as part of signalling pathways.Journal of the Royal Society, Interface · 2018Article
- Dynamics of Posttranslational Modification Systems: Recent Progress and Future Directions.Biophysical journal · 2018Review
- The Design Space of the Embryonic Cell Cycle Oscillator.Biophysical journal · 2017Article
- Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Multisite phosphorylation cycles are ubiquitous in cell regulation systems and are studied at multiple levels of complexity, from molecules to organisms, with the ultimate goal of establishing predictive understanding of the effects of genetic and pharmacological perturbations of protein phosphorylation in vivo. Achieving this goal is essentially impossible without mathematical models, which provide a systematic framework for exploring dynamic interactions of multiple network components. Most of the models studied to date do not discriminate between the distinct partially phosphorylated forms and focus on two limiting reaction regimes, distributive and processive, which differ in the number of enzyme-substrate binding events needed for complete phosphorylation or dephosphorylation. Here we use a minimal model of extracellular signal-related kinase regulation to explore the dynamics of a reaction network that includes all essential phosphorylation forms and arbitrary levels of reaction processivity. In addition to bistability, which has been studied extensively in distributive mechanisms, this network can generate periodic oscillations. Both bistability and oscillations can be realized at high levels of reaction processivity. Our work provides a general framework for systematic analysis of dynamics in multisite phosphorylation systems.
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