ArticleBiophysical journal2013
Tunable signal processing through a kinase control cycle: the IKK signaling node.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- A computational workflow for assessing drug effects on temporal signaling dynamics reveals robustness in stimulus-specific NFκB signaling.PLoS computational biology · 2025Article
- Article
- Dual-specific autophosphorylation of kinase IKK2 enables phosphorylation of substrate IκBα through a phosphoenzyme intermediate.bioRxiv : the preprint server for biology · 2025Article
- HDX-MS Analysis of Catalytic Activation of IKK2 in the IκB Kinase Complex.Biochemistry · 2024Article
- Processing stimulus dynamics by the NF-κB network in single cells.Experimental & molecular medicine · 2023Review
- Tonic TNF conditioning of macrophages safeguards stimulus-specific inflammatory responses.EMBO reports · 2023Article
- Ginaton reduces M1-polarized macrophages in hypertensive cardiac remodelingFrontiers in pharmacology · 2023Article
- NF-κB memory coordinates transcriptional responses to dynamic inflammatory stimuli.Cell reports · 2022Article
- Review
- Frequency-preference response in covalent modification cycles under substrate sequestration conditions.NPJ systems biology and applications · 2021Article
- NF-κB responds to absolute differences in cytokine concentrations.Science signaling · 2021Article
- Stimulus-specificity in the Responses of Immune Sentinel Cells.Current opinion in systems biology · 2019Article
- Signaling Crosstalk Mechanisms That May Fine-Tune Pathogen-Responsive NFκB.Frontiers in immunology · 2019Review
- Sensitivity analysis for reproducible candidate values of model parameters in signaling hub model.PloS one · 2019Article
- Active dendrites regulate the spatiotemporal spread of signaling microdomains.PLoS computational biology · 2018Article
- A novel allosteric inhibitor that prevents IKKβ activation.MedChemComm · 2018Article
- Model-based identification of TNFα-induced IKKβ-mediated and IκBα-mediated regulation of NFκB signal transduction as a tool to quantify the impact of drug-induced liver injury compounds.NPJ systems biology and applications · 2018Article
- Immune Response Signaling: Combinatorial and Dynamic Control.Trends in immunology · 2016Article
- Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states.Nature communications · 2016Article
- Signaling via the NFκB system.Wiley interdisciplinary reviews. Systems biology and medicine · 2016Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The transcription factor NFκB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. Those dynamics are thought to play a role in controlling the physiological response to cytokines and pathogens. Biochemical evidence suggests that the NFκB inducing kinase, IKK, a signaling hub onto which many signaling pathways converge, is regulated via a regulatory cycle comprising a poised, an active, and an inactive state. We hypothesize that it operates as a modulator of signal dynamics, actively reshaping the signals generated at the receptor proximal level. Here we show that a regulatory cycle can function in at least three dynamical regimes, tunable by regulating a single kinetic parameter. In particular, the simplest three-state regulatory cycle can generate signals with two well-defined phases, each with distinct coding capabilities in terms of the information they can carry about the stimulus. We also demonstrate that such a kinase cycle can function as a signal categorizer classifying diverse incoming signals into outputs with a limited set of temporal activity profiles. Finally, we discuss the extension of the results to other regulatory motifs that could be understood in terms of the regimes of the three-state cycle.
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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.