Simple biochemical pathways far from steady state can provide switchlike and integrated responses.

TitleSimple biochemical pathways far from steady state can provide switchlike and integrated responses.
Publication TypeJournal Article
Year of Publication2014
AuthorsDi Talia, S, Wieschaus, EF
JournalBiophys J
Volume107
Issue3
PaginationL1-L4
Date Published2014 Aug 05
ISSN1542-0086
KeywordsEnzymes, Kinetics, Models, Biological, Protein Processing, Post-Translational, Receptors, Cell Surface, Signal Transduction
Abstract

<p>Covalent modification cycles (systems in which the activity of a substrate is regulated by the action of two opposing enzymes) and ligand/receptor interactions are ubiquitous in signaling systems and their steady-state properties are well understood. However, the behavior of such systems far from steady state remains unclear. Here, we analyze the properties of covalent modification cycles and ligand/receptor interactions driven by the accumulation of the activating enzyme and the ligand, respectively. We show that for a large range of parameters both systems produce sharp switchlike response and yet allow for temporal integration of the signal, two desirable signaling properties. Ultrasensitivity is observed also in a region of parameters where the steady-state response is hyperbolic. The temporal integration properties are tunable by regulating the levels of the deactivating enzyme and receptor, as well as by adjusting the rate of accumulation of the activating enzyme and ligand. We propose that this tunability is used to generate precise responses in signaling systems.</p>

DOI10.1016/j.bpj.2014.06.018
Alternate JournalBiophys. J.
PubMed ID25099818
PubMed Central IDPMC4129562
Grant ListR00 HD074670 / HD / NICHD NIH HHS / United States
K99 HD074670 / HD / NICHD NIH HHS / United States
1K99HD074670 / HD / NICHD NIH HHS / United States
5R37HD15587 / HD / NICHD NIH HHS / United States
R37 HD015587 / HD / NICHD NIH HHS / United States
/ / Howard Hughes Medical Institute / United States