Determinants of Cell-to-Cell Variability in Protein Kinase Signaling
Figure 4
Cell-to-cell variability of cascades with a localized switch at the terminal level.
A Simulations show that pronounced variability for both (defined as the stimulus for a half-maximal pathway activation) and
. The concepts and parameter values correspond to Figure 1B, and the simulations were performed by iteratively applying Eqs. 16 and 17 with a Hill coefficient
(Supplemental Table S1). Colored box plots represent the
and
distribution of the ultrasensitive model, while gray box plots show the behavior of the reference gradual cascade (cf. Figure 1B). B The variabilities of a cascade with a localized switch at the terminal level were analyzed using the IQRatio, and the activation resistance was tuned by varying several phosphatase rate constants (
–
, thick, solid lines), and compared to a gradual model (thin, dashed lines). In contrast to a cascade with distributed ultrasensitivity (Figure 3D), homogeneous switching of all cells at a defined stimulus value is not possible even for low activation resistances. Similar results are obtained using the coefficient of variation as a measure of variability (Figure S4).