Ultrasensitization Due to Synexpression within a Signaling Cascade

<div><p>(A) Schematic representation of a signaling cascade subject to synexpression. An increase in the regulator, r, was assumed to result in a proportional increase in the expression of intermediates S and T, both of which are subject to covalent modification by (de)phosphorylation.</p><p>(B) Ultrasensitization due to synexpression within a signaling cascade measured numerically by plotting the normalized response as a function of the regulator concentration, r, where S_tot = T_tot = r (solid line). To show that synexpression enhances ultrasensitization, the case where the regulator, r, affects transcription of T only is also shown for S_tot = 10 (dashed line). Similar results were obtained for other values of S_tot or other stimulus strengths (data not shown). Parameters chosen: k_off,1 = k_off,5 = k_cat,2 = k_cat,6 = k_off,3 = k_off,7 = k_cat,8 = P_S,tot = P_T,tot = 1; k_on,1 = 0.02; k_on,5 = 0.2; k_on,3 = 2.1; k_on,7 = 2; k_cat,4 = 1.1; K_tot = 10.</p>