ArticleBiophysical journal2010
A combination of multisite phosphorylation and substrate sequestration produces switchlike responses.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- ERK inhibits Capicua repressor function via multisite phosphorylation.Journal of cell science · 2026Article
- Dynamics and Sensitivity of Signaling Pathways.Current pathobiology reports · 2022Article
- Intrinsic Disorder in the T Cell Receptor Creates Cooperativity and Controls ZAP70 Binding.Biophysical journal · 2021Article
- Exploring cyclic networks of multisite modification reveals origins of information processing characteristics.Scientific reports · 2020Article
- Effect of magnitude and variability of energy of activation in multisite ultrasensitive biochemical processes.PLoS computational biology · 2020Article
- The Influence of Molecular Reach and Diffusivity on the Efficacy of Membrane-Confined Reactions.Biophysical journal · 2019Article
- Exploring the intrinsic behaviour of multisite phosphorylation systems as part of signalling pathways.Journal of the Royal Society, Interface · 2018Article
- The effect of site-to-site variability in ultrasensitive dose responses.Journal of mathematical biology · 2017Article
- Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation.Science (New York, N.Y.) · 2016Article
- JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships.Microbiology and molecular biology reviews : MMBR · 2016Review
- Multisite Phosphorylation Modulates the T Cell Receptor ζ-Chain Potency but not the Switchlike Response.Biophysical journal · 2016Article
- Ultrasensitivity in independent multisite systems.Journal of mathematical biology · 2014Article
- Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs).Chemical reviews · 2014Review
- Enhancement of tunability of MAPK cascade due to coexistence of processive and distributive phosphorylation mechanisms.Biophysical journal · 2014Article
- Compact modeling of allosteric multisite proteins: application to a cell size checkpoint.PLoS computational biology · 2014Article
- Dynamics of posttranslational modifications of p53.Computational and mathematical methods in medicine · 2014Article
- Article
- Biphasic responses in multi-site phosphorylation systems.Journal of the Royal Society, Interface · 2013Article
- Ultrasensitivity by molecular titration in spatially propagating enzymatic reactions.Biophysical journal · 2013Article
- Ultrasensitive response motifs: basic amplifiers in molecular signalling networks.Open biology · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The phosphorylation of a protein on multiple sites has been proposed to promote the switchlike regulation of protein activity. Recent theoretical work, however, indicates that multisite phosphorylation, by itself, is less effective at creating switchlike responses than had been previously thought. The phosphorylation of a protein often alters its spatial localization, or its association with other proteins, and this sequestration can alter the accessibility of the substrate to the relevant kinases and phosphatases. Sequestration thus has the potential to interact with multisite phosphorylation to modulate ultrasensitivity and threshold. Here, using simple ordinary differential equations to represent phosphorylation, dephosphorylation, and binding/sequestration, we demonstrate that the combination of multisite phosphorylation and regulated substrate sequestration can produce a response that is both a good threshold and a good switch. Several strategies are explored, including both stronger and weaker sequestration with successive phosphorylations, as well as combinations that are more elaborate. In some strategies, such as when phosphorylation and dephosphorylation are segregated, a near-optimal switch is possible, where the effective Hill number equals the number of phosphorylation sites.
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Registered trials
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.