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notes: Sarma2012 - Oscillations in MAPK cascade (S1) Two plausible designs (S1 and S2) of coupled positive and negative feedback loops of MAPK cascade has been described in this paper. This model corresponds to model S1 that comprises negative feedback from MK-PP to MKKK-P layer coupled to positive feedback from MK-PP to MKK-PP layer. This model is described in the article: Oscillations in MAPK cascade triggered by two distinct designs of coupled positive and negative feedback loops. Sarma U, Ghosh I. BMC Res Notes. 2012 Jun 13;5:287. Abstract: BACKGROUND: Feedback loops, both positive and negative are embedded in the Mitogen Activated Protein Kinase (MAPK) cascade. In the three layer MAPK cascade, both feedback loops originate from the terminal layer and their sites of action are either of the two upstream layers. Recent studies have shown that the cascade uses coupled positive and negative feedback loops in generating oscillations. Two plausible designs of coupled positive and negative feedback loops can be elucidated from the literature; in one design the positive feedback precedes the negative feedback in the direction of signal flow and vice-versa in another. But it remains unexplored how the two designs contribute towards triggering oscillations in MAPK cascade. Thus it is also not known how amplitude, frequency, robustness or nature (analogous/digital) of the oscillations would be shaped by these two designs. RESULTS: We built two models of MAPK cascade that exhibited oscillations as function of two underlying designs of coupled positive and negative feedback loops. Frequency, amplitude and nature (digital/analogous) of oscillations were found to be differentially determined by each design. It was observed that the positive feedback emerging from an oscillating MAPK cascade and functional in an external signal processing module can trigger oscillations in the target module, provided that the target module satisfy certain parametric requirements. The augmentation of …
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