Exact analysis of intrinsic qualitative features of phosphorelays using mathematical models

Research output: Contribution to journalJournal articleResearchpeer-review

Phosphorelays are a class of signaling mechanisms used by cells to respond to changes in their environment. Phosphorelays (of which two-component systems constitute a special case) are particularly abundant in prokaryotes and have been shown to be involved in many fundamental processes such as stress response, osmotic regulation, virulence, and chemotaxis. We develop a general model of phosphorelays extending existing models of phosphorelays and two-component systems. We analyze the model analytically under the assumption of mass-action kinetics and prove that a phosphorelay has a unique stable steady-state. Furthermore, we derive explicit functions relating stimulus to the response in any layer of a phosphorelay and show that a limited degree of ultrasensitivity in the bottom layer of a phosphorelay is an intrinsic feature which does not depend on any reaction rates or substrate amounts. On the other hand, we show how adjusting reaction rates and substrate amounts may lead to higher degrees of ultrasensitivity in intermediate layers. The explicit formulas also enable us to prove how the response changes with alterations in stimulus, kinetic parameters, and substrate amounts. Aside from providing biological insight, the formulas may also be used to replace the time-consuming simulations in numerical analyses.
Original languageEnglish
JournalJournal of Theoretical Biology
Pages (from-to)7-18
Number of pages12
Publication statusPublished - 2012

    Research areas

  • Models, Biological, Phosphates, Phosphorylation, Prokaryotic Cells, Protein Kinases, Signal Transduction, Systems Theory

ID: 40285214