Exact analysis of intrinsic qualitative features of phosphorelays using mathematical models
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Exact analysis of intrinsic qualitative features of phosphorelays using mathematical models. / Knudsen, Michael; Feliu, Elisenda; Wiuf, Carsten.
I: Journal of Theoretical Biology, Bind 300, 2012, s. 7-18.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Exact analysis of intrinsic qualitative features of phosphorelays using mathematical models
AU - Knudsen, Michael
AU - Feliu, Elisenda
AU - Wiuf, Carsten
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Models, Biological
KW - Phosphates
KW - Phosphorylation
KW - Prokaryotic Cells
KW - Protein Kinases
KW - Signal Transduction
KW - Systems Theory
U2 - 10.1016/j.jtbi.2012.01.007
DO - 10.1016/j.jtbi.2012.01.007
M3 - Journal article
C2 - 22266661
VL - 300
SP - 7
EP - 18
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
SN - 0022-5193
ER -
ID: 40285214