ArticleProceedings of the National Academy of Sciences of the United States of America2003
Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed.
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- Relationship Between Dimensionality and Convergence of Optimization Algorithms: A Comparison Between Data-Driven Normalization and Scaling Factor-Based Methods Using PEPSSBI.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms.Metabolites · 2021Review
- Identifiability analysis for stochastic differential equation models in systems biology.Journal of the Royal Society, Interface · 2020Article
- Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction.Molecular systems biology · 2020Article
- Benchmark problems for dynamic modeling of intracellular processes.Bioinformatics (Oxford, England) · 2019Article
- Identification of a time-varying intracellular signalling model through data clustering and parameter selection: application to NF-[inline-formula removed]B signalling pathway induced by LPS in the presence of BFA.IET systems biology · 2019Article
- Time-dependent antagonist-agonist switching in receptor tyrosine kinase-mediated signaling.BMC bioinformatics · 2019Article
- Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling.Communications biology · 2019Article
- Hierarchical optimization for the efficient parametrization of ODE models.Bioinformatics (Oxford, England) · 2018Article
- An information-theoretic framework for deciphering pleiotropic and noisy biochemical signaling.Nature communications · 2018Article
- Bayesian parameter estimation for biochemical reaction networks using region-based adaptive parallel tempering.Bioinformatics (Oxford, England) · 2018Article
- Optimization and profile calculation of ODE models using second order adjoint sensitivity analysis.Bioinformatics (Oxford, England) · 2018Article
- The competitive nature of signal transducer and activator of transcription complex formation drives phenotype switching of T cells.Immunology · 2018Article
- Correlated receptor transport processes buffer single-cell heterogeneity.PLoS computational biology · 2017Article
29 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
Considerable progress has been made in identifying the molecular composition of complex signaling networks controlling cell proliferation, differentiation, and survival. However, to discover general building principles and predict the dynamic behavior of signaling networks, it is necessary to develop quantitative models based on experimental observations. Here we report a mathematical model of the core module of the Janus family of kinases (JAK)-signal transducer and activator of transcription (STAT) signaling pathway based on time-resolved measurements of receptor and STAT5 phosphorylation. Applying the fitted model, we can determine the quantitative behavior of STAT5 populations not accessible to experimental measurement. By in silico investigations, we identify the parameters of nuclear shuttling as the most sensitive to perturbations and verify experimentally the model prediction that inhibition of nuclear export results in a reduced transcriptional yield. The model reveals that STAT5 undergoes rapid nucleocytoplasmic cycles, continuously coupling receptor activation and target gene transcription, thereby forming a remote sensor between nucleus and receptor. Thus, dynamic modeling of signaling pathways can promote functional understanding at the systems level.
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