Schematic representation of the cascades S1 and S2. The MAPK cascades embedded in two differential designs of positive and negative feedback loops are shown here. (A) An external signal ‘Signal’ activates the cascade S1 by triggering the phosphorylation of M3K. The cascade is embedded in the feedback design PN-I. Negative feedback from MK** to M3K layer is shown with a red bar with blunt head and positive feedback from MK** to M2K layer is shown with blue arrows. (B) The external signal ‘Signal’ triggers M3K phosphorylation and the cascade S2 embedded in the feedback design PN-II is activated. Positive feedback from MK** to the M3K layer and negative feedback from MK** to the M2K layer are shown as blue arrow and red bars, respectively.