%0 Journal Article
%T Oscillations in MAPK cascade triggered by two distinct designs of coupled positive and negative feedback loops
%A Uddipan Sarma
%A Indira Ghosh
%J BMC Research Notes
%D 2012
%I BioMed Central
%R 10.1186/1756-0500-5-287
%X 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 the two models was done to incorporate the nuclear-cytoplasmic shuttling of cascade components followed by induction of a nuclear phosphatase. It revealed that the fate of oscillations in the MAPK cascade is governed by the feedback designs. Oscillations were unaffected due to nuclear compartmentalization owing to one design but were completely abolished in the other case.The MAPK cascade can utilize two distinct designs of coupled positive and negative feedback loops to trigger oscillations. The amplitude, frequency and robustness of the oscillations in presence or absence of nuclear compartmentalization were differentially determined by two designs of coupled positive and negative feedback loops. A positive feedback from an oscillating MAPK cascade was shown to induce oscillations in an external signal processing module, uncovering a novel regulatory aspect of MAPK signal processing.Signal transduction pathways such as the Mitogen Activated Protein Kinase (MAPK) cascade responds to wide range of external stimuli to trigger growth, cell-division and proliferation [1,2]. The evolutionarily conserved structure of the three layer MAPK cascade consists of the MAPKKK (henceforth referred as M3K), MAPKK (henceforth referred as M2K) and MAPK (henceforth referred as MK) from yeast to human, which processes the incoming signal through a series of covalent modification cycles [1]. M3K is activated upon single phosphorylation wh
%U http://www.biomedcentral.com/1756-0500/5/287