000181255 001__ 181255
000181255 005__ 20190316235456.0
000181255 0247_ $$2doi$$a10.1088/1478-3975/9/4/045010
000181255 022__ $$a1478-3975
000181255 02470 $$2ISI$$a000307522200011
000181255 037__ $$aARTICLE
000181255 245__ $$aExploration of trade-offs between steady-state and dynamic properties in signaling cycles
000181255 269__ $$a2012
000181255 260__ $$bIop Publishing Ltd$$c2012$$aBristol
000181255 300__ $$a13
000181255 336__ $$aJournal Articles
000181255 520__ $$aIn the intracellular signaling networks that regulate important cell processes, the base pattern comprises the cycle of reversible phosphorylation of a protein, catalyzed by kinases and opposing phosphatases. Mathematical modeling and analysis have been used for gaining a better understanding of their functions and to capture the rules governing system behavior. Since biochemical parameters in signaling pathways are not easily accessible experimentally, it is necessary to explore possibilities for both steady-state and dynamic responses in these systems. While a number of studies have focused on analyzing these properties separately, it is necessary to take into account both of these responses simultaneously in order to be able to interpret a broader range of phenotypes. This paper investigates the trade-offs between optimal characteristics of both steady-state and dynamic responses. Following an inverse sensitivity analysis approach, we use systematic optimization methods to find the biochemical and biophysical parameters that simultaneously achieve optimal steady-state and dynamic performance. Remarkably, we find that even a single covalent modification cycle can simultaneously and robustly achieve high ultrasensitivity, high amplification and rapid signal transduction. We also find that the response rise and decay times can be modulated independently by varying the activating- and deactivating-enzyme-to-interconvertible-protein ratios.
000181255 6531_ $$asignaling
000181255 6531_ $$aoptimization
000181255 6531_ $$aMAPK
000181255 6531_ $$aultrasensitivity
000181255 700__ $$0242463$$g182211$$aRadivojevic, A.
000181255 700__ $$aChachuat, B.
000181255 700__ $$0240449$$g104596$$aBonvin, D.
000181255 700__ $$0240657$$g174688$$aHatzimanikatis, V.
000181255 773__ $$j9$$tPhysical Biology$$k4$$q045010
000181255 8564_ $$uhttp://iopscience.iop.org/1478-3975/9/4/045010$$zURL
000181255 8564_ $$uhttps://infoscience.epfl.ch/record/181255/files/AR_2012.pdf$$zPublisher's version$$s853186$$yPublisher's version
000181255 909C0 $$xU11422$$0252131$$pLCSB
000181255 909C0 $$0252053$$pLA
000181255 909CO $$qGLOBAL_SET$$pSB$$pSTI$$particle$$ooai:infoscience.tind.io:181255
000181255 917Z8 $$x104596
000181255 917Z8 $$x104596
000181255 917Z8 $$x174688
000181255 937__ $$aEPFL-ARTICLE-181255
000181255 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000181255 980__ $$aARTICLE