Figure 11.

Rate limiting steps controlling most effectively the transcriptional readouts of Tnfα and Cxcl10. Schematic representations on rate limiting steps inferred from non-orthogonal perturbation experiments. The analysis indicates that the two transcriptional outputs modulated by the canonical signaling network are differentially controlled. It is inferred that the transcriptional readout of Tnfα is collectivelly controlled by the whole integrated reaction system; whereas the the transcriptional readout of Cxcl10 is most effectively controlled by only a tiny fraction of the biochemical reactions involved in signal propagation, which are quantitatively modulated by just few internal reaction parameters. For example, it was found that the Dissociation Rate of IκB-NFκB (k21cat), the Import Rate to Nucleus of NFκB (k22f), and the set of parameteres involved in transcriptional activation, seem to most effectively control this signaling ouput. The bright red arrow is to illustrate that the signaling flow that eventually leads to the transcriptional activation of Tnfα is tightly controlled by the whole integrated reaction network. The dull yellow arrow indicates that all reaction steps in the network, except those for which the parameters are illustrated, are not critically involved in controlling the transcriptional readout of Cxcl10.