Enzyme-sharing as a cause of multi-stationarity in signalling systems
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Enzyme-sharing as a cause of multi-stationarity in signalling systems. / Feliu, Elisenda; Wiuf, Carsten.
In: Journal of the Royal Society. Interface, Vol. 9, No. 71, 2012, p. 1224-1232.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 40285267