On sensitivity amplification in intracellular signaling cascades.
Sensitivity amplification has long been regarded as a virtually universal property of signal transduction cascades, yet a comprehensive parameter analysis remains a challenge even for relatively simple networks. We use a fast and accurate method to compute properties of multilevel cascades of activation-inactivation cycles and show that the monocyclic cascades amplify sensitivity only under specific conditions. In particular, it is found that efficient sensitivity amplification in a cascade, relative to the sensitivities of individual cycles, requires asymmetry in saturation of converter enzymes, with inhibitors much more saturated than activators.
Rácz
Eva
E
Institute of Physics, Budapest University of Technology and Economics, H-1111 Budapest, Hungary. re551@hszk.bme.hu
Slepchenko
Boris M
BM
D000465:Algorithms; D003198:Computer Simulation; D005246:Feedback / Q000502:physiology; D042541:Intracellular Space / Q000378:metabolism*; D008954:Models, Biological; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*