ArticleMolecular systems biology2012
Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast.
Article in Molecular systems biology, 2012. 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, 67 citations in OpenAlex.
- Yeast cell responses and survival during periodic osmotic stress are controlled by glucose availability.eLife · 2024Article
- Data integration strategies for whole-cell modeling.FEMS yeast research · 2024Review
- Strong delayed negative feedback.Frontiers in network physiology · 2024Article
- Positive feedback induces switch between distributive and processive phosphorylation of Hog1.Nature communications · 2023Article
- Building predictive signaling models by perturbing yeast cells with time-varying stimulations resulting in distinct signaling responses.STAR protocols · 2021Article
- Article
- Negative feedback-loop mechanisms regulating HOG- and pheromone-MAPK signaling in yeast.Current genetics · 2020Review
- Osmostress enhances activating phosphorylation of Hog1 MAP kinase by mono-phosphorylated Pbs2 MAP2K.The EMBO journal · 2020Article
- Effects of Post-translational Modifications on Membrane Localization and Signaling of Prostanoid GPCR-G Protein Complexes and the Role of Hypoxia.The Journal of membrane biology · 2019Review
- Short linear motifs in intrinsically disordered regions modulate HOG signaling capacity.BMC systems biology · 2018Article
- Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction.PLoS computational biology · 2018Article
- Quantitative interactome of a membrane Bcl-2 network identifies a hierarchy of complexes for apoptosis regulation.Nature communications · 2017Article
- Article
- Predicting network modules of cell cycle regulators using relative protein abundance statistics.BMC systems biology · 2017Article
- Spatial and temporal signal processing and decision making by MAPK pathways.The Journal of cell biology · 2017Review
- Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus.PloS one · 2017Article
- How time delay and network design shape response patterns in biochemical negative feedback systems.BMC systems biology · 2016Article
- Systems Level Analysis of the Yeast Osmo-Stat.Scientific reports · 2016Article
- Ultrasensitive Negative Feedback Control: A Natural Approach for the Design of Synthetic Controllers.PloS one · 2016Article
- A Thermodynamic Model of Monovalent Cation Homeostasis in the Yeast Saccharomyces cerevisiae.PLoS computational biology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype signalling system for eukaryotes. We used an unprecedented amount of data to parameterise 192 models capturing different hypotheses about molecular mechanisms underlying osmo-adaptation and selected a best approximating model. This model implied novel mechanisms regulating osmo-adaptation in yeast. The model suggested that (i) the main mechanism for osmo-adaptation is a fast and transient non-transcriptional Hog1-mediated activation of glycerol production, (ii) the transcriptional response serves to maintain an increased steady-state glycerol production with low steady-state Hog1 activity, and (iii) fast negative feedbacks of activated Hog1 on upstream signalling branches serves to stabilise adaptation response. The best approximating model also indicated that homoeostatic adaptive systems with two parallel redundant signalling branches show a more robust and faster response than single-branch systems. We corroborated this notion to a large extent by dedicated measurements of volume recovery in single cells. Our study also demonstrates that systematically testing a model ensemble against data has the potential to achieve a better and unbiased understanding of molecular mechanisms.
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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.