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