ArticleCurrent biology : CB2020
Inference of Multisite Phosphorylation Rate Constants and Their Modulation by Pathogenic Mutations.
Article in Current biology : CB, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Real time characterization of the MAPK pathway using native mass spectrometry.Communications biology · 2025Article
- Mathematical Modeling and Inference of Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Cell Signaling Pathways.International journal of molecular sciences · 2024Review
- Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.NPJ systems biology and applications · 2024Article
- Kinetics of diffusion-influenced multisite phosphorylation with enzyme reactivation.Biopolymers · 2024Article
- Evolutionary history of MEK1 illuminates the nature of deleterious mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Stochastic phenotypes in RAS-dependent developmental diseases.Current biology : CB · 2023Article
- Algebra, Geometry and Topology of ERK Kinetics.Bulletin of mathematical biology · 2022Article
- On the parameter combinations that matter and on those that do not: data-driven studies of parameter (non)identifiability.PNAS nexus · 2022Article
- Parameter estimation and uncertainty quantification using information geometry.Journal of the Royal Society, Interface · 2022Review
- MECHANISTIC AND DATA-DRIVEN MODELS OF CELL SIGNALING: TOOLS FOR FUNDAMENTAL DISCOVERY AND RATIONAL DESIGN OF THERAPY.Current opinion in systems biology · 2021Article
- Molecular mechanisms underlying cellular effects of human MEK1 mutations.Molecular biology of the cell · 2021Article
- Multisite reversible association in membranes and solutions: From non-Markovian to Markovian kinetics.The Journal of chemical physics · 2020Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Multisite protein phosphorylation plays a critical role in cell regulation [1-3]. It is widely appreciated that the functional capabilities of multisite phosphorylation depend on the order and kinetics of phosphorylation steps, but kinetic aspects of multisite phosphorylation remain poorly understood [4-6]. Here, we focus on what appears to be the simplest scenario, when a protein is phosphorylated on only two sites in a strict, well-defined order. This scenario describes the activation of ERK, a highly conserved cell-signaling enzyme. We use Bayesian parameter inference in a structurally identifiable kinetic model to dissect dual phosphorylation of ERK by MEK, a kinase that is mutated in a large number of human diseases [7-12]. Our results reveal how enzyme processivity and efficiencies of individual phosphorylation steps are altered by pathogenic mutations. The presented approach, which connects specific mutations to kinetic parameters of multisite phosphorylation mechanisms, provides a systematic framework for closing the gap between studies with purified enzymes and their effects in the living organism.
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