Enzyme-sharing as a cause of multi-stationarity in signalling systems
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Multi-stationarity in biological systems is a mechanism of cellular decision-making. In particular, signalling pathways regulated by protein phosphorylation display features that facilitate a variety of responses to different biological inputs. The features that lead to multi-stationarity are of particular interest to determine, as well as the stability, properties of the steady states. In this paper, we determine conditions for the emergence of multi-stationarity in small motifs without feedback that repeatedly occur in signalling pathways. We derive an explicit mathematical relationship ¿ between the concentration of a chemical species at steady state and a conserved quantity of the system such as the total amount of substrate available. We show that ¿ determines the number of steady states and provides a necessary condition for a steady state to be stable-that is, to be biologically attainable. Further, we identify characteristics of the motifs that lead to multi-stationarity, and extend the view that multi-stationarity in signalling pathways arises from multi-site phosphorylation. Our approach relies on mass-action kinetics, and the conclusions are drawn in full generality without resorting to simulations or random generation of parameters. The approach is extensible to other systems.
|Journal of the Royal Society. Interface
|Number of pages
|Published - 2012
- Animals, Binding Sites, Computer Simulation, Enzyme Activation, Enzymes, Humans, Models, Biological, Models, Statistical, Protein Binding, Signal Transduction