ArticlePLoS computational biology2007
Operating regimes of signaling cycles: statics, dynamics, and noise filtering.
Article in PLoS computational biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed.
- Generating synthetic signaling networks for in silico modeling studies.Journal of theoretical biology · 2024Article
- First-order ultrasensitivity in phosphorylation cycles.Interface focus · 2024Article
- Protein-protein complexes can undermine ultrasensitivity-dependent biological adaptation.Journal of the Royal Society, Interface · 2023Article
- Dynamics and Sensitivity of Signaling Pathways.Current pathobiology reports · 2022Article
- Article
- Crosstalk and ultrasensitivity in protein degradation pathways.PLoS computational biology · 2020Article
- Misuse of the Michaelis-Menten rate law for protein interaction networks and its remedy.PLoS computational biology · 2020Review
- Bayesian modeling reveals metabolite-dependent ultrasensitivity in the cyanobacterial circadian clock.Molecular systems biology · 2020Article
- The Design Principles of Biochemical Timers: Circuits that Discriminate between Transient and Sustained Stimulation.Cell systems · 2019Article
- Article
- Intrinsic limits of information transmission in biochemical signalling motifs.Interface focus · 2018Article
- Properties of cell signaling pathways and gene expression systems operating far from steady-state.Scientific reports · 2018Article
- When More Is Less: Dual Phosphorylation Protects Signaling Off State against Overexpression.Biophysical journal · 2018Article
- Computing Mathematical Functions using DNA via Fractional Coding.Scientific reports · 2018Article
- Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity.Biophysical journal · 2017Article
- Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations.PloS one · 2017Article
- Signaling cascades transmit information downstream and upstream but unlikely simultaneously.BMC systems biology · 2016Article
- Review
- Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry.Journal of biological engineering · 2016Article
- Ultrasensitive Negative Feedback Control: A Natural Approach for the Design of Synthetic Controllers.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
A ubiquitous building block of signaling pathways is a cycle of covalent modification (e.g., phosphorylation and dephosphorylation in MAPK cascades). Our paper explores the kind of information processing and filtering that can be accomplished by this simple biochemical circuit. Signaling cycles are particularly known for exhibiting a highly sigmoidal (ultrasensitive) input-output characteristic in a certain steady-state regime. Here, we systematically study the cycle's steady-state behavior and its response to time-varying stimuli. We demonstrate that the cycle can actually operate in four different regimes, each with its specific input-output characteristics. These results are obtained using the total quasi-steady-state approximation, which is more generally valid than the typically used Michaelis-Menten approximation for enzymatic reactions. We invoke experimental data that suggest the possibility of signaling cycles operating in one of the new regimes. We then consider the cycle's dynamic behavior, which has so far been relatively neglected. We demonstrate that the intrinsic architecture of the cycles makes them act--in all four regimes--as tunable low-pass filters, filtering out high-frequency fluctuations or noise in signals and environmental cues. Moreover, the cutoff frequency can be adjusted by the cell. Numerical simulations show that our analytical results hold well even for noise of large amplitude. We suggest that noise filtering and tunability make signaling cycles versatile components of more elaborate cell-signaling pathways.
Indexed as
Identifiers
What OpenQuestion holds
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.