Frequency preference in covalent modification cycles under sequestration conditions

JULIANA REVES SZEMERE; ALEJANDRA C VENTURA; HORACIO G ROTSTEIN

Buenos Aires

Conferencia; 27th IUPAP International Conference on Statistical Physics, StatPhys27; 2019

IUPAP C3 Commission, Statistical Physics

Covalent modification cycles (CMCs) are basic units of signaling systems and their properties are well understood. However, the behavior of such systems has been mostly characterized in situations where the modifying enzymes are saturated by the substrate. Experimental data on protein abundance suggest that the enzymes and their target proteins are present in comparable concentrations, leading to a different scenario in which the substrate is mostly sequestered by the enzymes. Related to this last condition, a type of response called signal termination was proposed in the literature, in which the modified substrate of the CMC is formed only for a certain amount of time, producing a transient response in the cycle. We here characterize the conditions leading to signal termination under constant stimulation in CMCs. In addition, we demonstrate that this behavior leads to a frequency preference when the cycle is subjected to periodic stimulation ,while the literature reports that CMCs behave as low pass filters. Altogether, signal termination and frequency preference are two important features in cell signaling that were overlooked in the literature associated to CMC. The evidence that, in conditions mimicking an in vivo scenario, enzymes and substrates are present in comparable concentrations suggests that these two properties may be ubiquitous in cell signaling systems.