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We mathematically modeled the receptor-activated MAP kinase signaling byincorporating the regulation through cellular phosphatases. Activation inducedthe alignment of a phosphatase cascade in parallel with the MAP kinase pathway.A novel regulatory motif was thus generated, providing for the combinatorialcontrol of each MAPK intermediate. This ensured a non-linear mode of signaltransmission with the output being shaped by the balance between the strengthof input signal, and the activity gradient along the phosphatase axis. Shiftsin this balance yielded modulations in topology of the motif, thereby expandingthe repertoire of output responses. Thus we identify an added dimension tosignal processing, wherein the output response to an external stimulus isadditionally filtered through indicators that define the phenotypic status ofthe cell.

Integration of a Phosphatase Cascade with the MAP Kinase Pathway provides for a Novel Signal Processing Function