TY - JOUR
T1 - Three level signal transduction cascades lead to reliably timed switches
AU - Armbruster, Hans
AU - Nagy, John
AU - Young, Jon
N1 - Funding Information:
This work was partially supported by More Graduate Education at Mountain States Alliance (MGE@MSA) , Alliance for Graduate Education and the Professoriate (AGEP) , National Science Foundation (NSF) Cooperative Agreement no. HRD-0450137 (to J.Y.) and by the Volkswagen Foundation under the program on Complex Networks (to D.A. and J.Y.).
PY - 2014/11/21
Y1 - 2014/11/21
N2 - Signaling cascades proliferate signals received on the cell membrane to the nucleus. While noise filtering, ultra-sensitive switches, and signal amplification have all been shown to be features of such signaling cascades, it is not understood why cascades typically show three or four layers. Using singular perturbation theory, Michaelis-Menten type equations are derived for open enzymatic systems. Cascading these equations we demonstrate that the output signal as a function of time becomes sigmoidal with the addition of more layers. Furthermore, it is shown that the activation time will speed up to a point, after which more layers become superfluous. It is shown that three layers create a reliable sigmoidal response progress curve from a wide variety of time-dependent signaling inputs arriving at the cell membrane, suggesting the evolutionary benefit of the observed cascades.
AB - Signaling cascades proliferate signals received on the cell membrane to the nucleus. While noise filtering, ultra-sensitive switches, and signal amplification have all been shown to be features of such signaling cascades, it is not understood why cascades typically show three or four layers. Using singular perturbation theory, Michaelis-Menten type equations are derived for open enzymatic systems. Cascading these equations we demonstrate that the output signal as a function of time becomes sigmoidal with the addition of more layers. Furthermore, it is shown that the activation time will speed up to a point, after which more layers become superfluous. It is shown that three layers create a reliable sigmoidal response progress curve from a wide variety of time-dependent signaling inputs arriving at the cell membrane, suggesting the evolutionary benefit of the observed cascades.
KW - MAP-kinase network
KW - Michaelis-Menten equations
KW - Time-dependent ODEs
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U2 - 10.1016/j.jtbi.2014.07.012
DO - 10.1016/j.jtbi.2014.07.012
M3 - Article
C2 - 25036439
AN - SCOPUS:84905856458
SN - 0022-5193
VL - 361
SP - 69
EP - 80
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
ER -