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Enzyme Localization Can Drastically Affect Signal Amplification in Signal Transduction Pathways
Figure 2
The Effect of Enzyme Localization on the Response of a Push–Pull Network
The input–output relation of the push–pull network shown in Figure 1 is plotted for different values of the total substrate concentration [S]T, for the case in which all components are uniformly distributed in space (A) and for the case in which the activating enzyme is located at one end of the cell, while the other components can diffuse freely through the cell (B). Here, 
. In (A) and (B), [Ed]T = 0.5 μM, KM,a = KM,d = 0.5 μM, and k3 = k6 = 25s−1. In (B), the diffusion constant is D = 10 μm2 s−1. The inset shows the logarithmic gain g ≡ ∂ln[X*]T / ∂ln[Ea]T. It is seen that the sharpness of the response increases markedly with increasing substrate concentration when all the components are uniformly distributed in space (A), but much less so when the activating enzyme Ea is located at one pole of the cell, while the deactivating enzyme Ea is distributed in the cytoplasm. When both enzymes Ea and Ed are located at one pole, the steady-state dose–response curve is identical to that in (A).
doi: https://doi.org/10.1371/journal.pcbi.0030195.g002