ArticleMolecular systems biology2009
Theoretical and experimental analysis links isoform-specific ERK signalling to cell fate decisions.
Article in Molecular systems biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 81 citations in OpenAlex.
- When More Is Less: Dual Phosphorylation Protects Signaling Off State against Overexpression.Biophysical journal · 2018Article
- 'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age.Mechanisms of ageing and development · 2018Article
- A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT.Oncotarget · 2017Article
- Sampling-based Bayesian approaches reveal the importance of quasi-bistable behavior in cellular decision processes on the example of the MAPK signaling pathway in PC-12 cell lines.BMC systems biology · 2017Article
- Protein abundance of AKT and ERK pathway components governs cell type-specific regulation of proliferation.Molecular systems biology · 2017Article
- High-Content Imaging Platform for Profiling Intracellular Signaling Network Activity in Living Cells.Cell chemical biology · 2016Article
- Identification of Cell Type-Specific Differences in Erythropoietin Receptor Signaling in Primary Erythroid and Lung Cancer Cells.PLoS computational biology · 2016Article
- miR-181a/b control the assembly of visual circuitry by regulating retinal axon specification and growth.Developmental neurobiology · 2015Article
- Sensitive targeted quantification of ERK phosphorylation dynamics and stoichiometry in human cells without affinity enrichment.Analytical chemistry · 2015Article
- SBMLSimulator: A Java Tool for Model Simulation and Parameter Estimation in Systems Biology.Computation (Basel, Switzerland) · 2014Article
- SensA: web-based sensitivity analysis of SBML models.Bioinformatics (Oxford, England) · 2014Article
- Forecasting cell death dose-response from early signal transduction responses in vitro.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- Optimal experiment design for model selection in biochemical networks.BMC systems biology · 2014Article
- Data-driven modeling reconciles kinetics of ERK phosphorylation, localization, and activity states.Molecular systems biology · 2014Article
- Kinetics of gene derepression by ERK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire.Immunologic research · 2013Review
- Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways.BMC systems biology · 2013Article
- Parameter trajectory analysis to identify treatment effects of pharmacological interventions.PLoS computational biology · 2013Article
- A novel mechanism for ERK-dependent regulation of IL4 transcription during human Th2-cell differentiation.Immunology and cell biology · 2012Article
- Short-term information processing, long-term responses: Insights by mathematical modeling of signal transduction. Early activation dynamics of key signaling mediators can be predictive for cell fate decisions.BioEssays : news and reviews in molecular, cellular and developmental biology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Cell fate decisions are regulated by the coordinated activation of signalling pathways such as the extracellular signal-regulated kinase (ERK) cascade, but contributions of individual kinase isoforms are mostly unknown. By combining quantitative data from erythropoietin-induced pathway activation in primary erythroid progenitor (colony-forming unit erythroid stage, CFU-E) cells with mathematical modelling, we predicted and experimentally confirmed a distributive ERK phosphorylation mechanism in CFU-E cells. Model analysis showed bow-tie-shaped signal processing and inherently transient signalling for cytokine-induced ERK signalling. Sensitivity analysis predicted that, through a feedback-mediated process, increasing one ERK isoform reduces activation of the other isoform, which was verified by protein over-expression. We calculated ERK activation for biochemically not addressable but physiologically relevant ligand concentrations showing that double-phosphorylated ERK1 attenuates proliferation beyond a certain activation level, whereas activated ERK2 enhances proliferation with saturation kinetics. Thus, we provide a quantitative link between earlier unobservable signalling dynamics and cell fate decisions.
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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.