title: Enzyme-sharing as a cause of multi-stationarity in signalling systems.
abstract: 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 ϕ 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 ϕ 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.
authors: Bioinformatics Research Centre, Aarhus University, C. F. Møllers Allé 8, 8000 Aarhus, Denmark.
authors: Elisenda
authors: E
authors: Feliu
authors: Carsten
authors: C
authors: Wiuf
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D004798:Enzymes