On sensitivity amplification in intracellular signaling cascades

Abstract

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.