TY - JOUR

T1 - Enzyme-sharing as a cause of multi-stationarity in signalling systems

AU - Feliu, Elisenda

AU - Wiuf, Carsten

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Computer Simulation

KW - Enzyme Activation

KW - Enzymes

KW - Humans

KW - Models, Biological

KW - Models, Statistical

KW - Protein Binding

KW - Signal Transduction

U2 - 10.1098/rsif.2011.0664

DO - 10.1098/rsif.2011.0664

M3 - Journal article

C2 - 22048944

VL - 9

SP - 1224

EP - 1232

JO - Journal of the Royal Society. Interface

JF - Journal of the Royal Society. Interface

SN - 1742-5689

IS - 71

ER -