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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Bibliographic Details
Published in:Scientific reports 2018-11, Vol.8 (1), p.17035-14, Article 17035
Main Authors: Di-Bella, Juan Pablo, Colman-Lerner, Alejandro, Ventura, Alejandra C.
Format: Article
Language:English
Subjects:
119/118
631/553/2695
639/705/1041
Cycle protein
Gene expression
Gene Expression Regulation
Humanities and Social Sciences
Ligands
multidisciplinary
Protein Binding
Science
Science (multidisciplinary)
Signal Transduction
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-34766-0