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Properties of cell signaling pathways and gene expression systems operating far from steady-state

Ligand-receptor systems, covalent modification cycles, and transcriptional networks are basic units of signaling systems and their steady-state properties are well understood. However, the behavior of such systems before steady-state is poorly characterized. Here, we analyzed the properties of input...

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Autores principales: Di-Bella, Juan Pablo, Colman-Lerner, Alejandro, Ventura, Alejandra C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242903/
https://www.ncbi.nlm.nih.gov/pubmed/30451879
http://dx.doi.org/10.1038/s41598-018-34766-0
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author Di-Bella, Juan Pablo
Colman-Lerner, Alejandro
Ventura, Alejandra C.
author_facet Di-Bella, Juan Pablo
Colman-Lerner, Alejandro
Ventura, Alejandra C.
author_sort Di-Bella, Juan Pablo
collection PubMed
description Ligand-receptor systems, covalent modification cycles, and transcriptional networks are basic units of signaling systems and their steady-state properties are well understood. However, the behavior of such systems before steady-state is poorly characterized. Here, we analyzed the properties of input-output curves for each of these systems as they approach steady-state. In ligand-receptor systems, the EC(50) (concentration of the ligand that occupies 50% of the receptors) is higher before the system reaches steady-state. Based on this behavior, we have previously defined PRESS (for pre-equilibrium sensing and signaling), a general “systems level” mechanism cells may use to overcome input saturation. Originally, we showed that, given a step stimulation, PRESS operates when the kinetics of ligand-receptor binding are slower than the downstream signaling steps. Now, we show that, provided the input increases slowly, it is not essential for the ligand binding reaction itself to be slow. In addition, we demonstrate that covalent modification cycles and gene expression systems may also operate in PRESS mode. Thus, nearly all biochemical processes may operate in PRESS mode, suggesting that this mechanism may be ubiquitous in cell signaling systems.
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spelling pubmed-62429032018-11-27 Properties of cell signaling pathways and gene expression systems operating far from steady-state Di-Bella, Juan Pablo Colman-Lerner, Alejandro Ventura, Alejandra C. Sci Rep Article Ligand-receptor systems, covalent modification cycles, and transcriptional networks are basic units of signaling systems and their steady-state properties are well understood. However, the behavior of such systems before steady-state is poorly characterized. Here, we analyzed the properties of input-output curves for each of these systems as they approach steady-state. In ligand-receptor systems, the EC(50) (concentration of the ligand that occupies 50% of the receptors) is higher before the system reaches steady-state. Based on this behavior, we have previously defined PRESS (for pre-equilibrium sensing and signaling), a general “systems level” mechanism cells may use to overcome input saturation. Originally, we showed that, given a step stimulation, PRESS operates when the kinetics of ligand-receptor binding are slower than the downstream signaling steps. Now, we show that, provided the input increases slowly, it is not essential for the ligand binding reaction itself to be slow. In addition, we demonstrate that covalent modification cycles and gene expression systems may also operate in PRESS mode. Thus, nearly all biochemical processes may operate in PRESS mode, suggesting that this mechanism may be ubiquitous in cell signaling systems. Nature Publishing Group UK 2018-11-19 /pmc/articles/PMC6242903/ /pubmed/30451879 http://dx.doi.org/10.1038/s41598-018-34766-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Di-Bella, Juan Pablo
Colman-Lerner, Alejandro
Ventura, Alejandra C.
Properties of cell signaling pathways and gene expression systems operating far from steady-state
title Properties of cell signaling pathways and gene expression systems operating far from steady-state
title_full Properties of cell signaling pathways and gene expression systems operating far from steady-state
title_fullStr Properties of cell signaling pathways and gene expression systems operating far from steady-state
title_full_unstemmed Properties of cell signaling pathways and gene expression systems operating far from steady-state
title_short Properties of cell signaling pathways and gene expression systems operating far from steady-state
title_sort properties of cell signaling pathways and gene expression systems operating far from steady-state
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242903/
https://www.ncbi.nlm.nih.gov/pubmed/30451879
http://dx.doi.org/10.1038/s41598-018-34766-0
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