Dynamics of MAPK cascade embedded in PN-I and PN-II. Both models S1 and S2 were simulated without any feedbacks, with negative feedback alone and with coupled positive and negative feedbacks. Without any feedback loop, both S1 and S2 shows full amplitude phosphorylation of MK**, M2K** and M3K* (A and D). The negative feedback from MK** to M3K phosphorylation in S1 [B] and from MK** to M2K phosphorylation in S2 (E) resulted in inhibition of MK** amplitude. The coupled feedback design PN-I in S1 (C) and PN-II in S2 triggered sustained oscillations (C &F).