Figure 10
Rate limiting steps controlling most effectively the global behavior of the canonical TLR4 signaling network. Schematic representation on rate limiting steps inferred from non-orthogonal perturbation experiments. The analysis indicates that the global behavior of the TLR4 signaling network is most effectively control by only few reaction steps along the signaling cascades. It is inferred that global information processing in the system heavily relies on 8 biochemical reaction processes, which are quantitatively modulated by just few internal reaction parameters. For instance, the global behavior of the network was found to be remarkably sensitive to random fluctuations in the reaction parameters controlling the Production and Degradation Rates of the TLR4 Susceptible Form (kps and kds), the Dephosphorylation Rate of IKKcp* (k 20), the association rate between the IKKcp* and IĪŗB-NFĪŗB (k 21f), the dissociation rate between the IKKcp* and IĪŗB-NFĪŗB, (k 21r), and the Dissociation Rate of IĪŗB-NFĪŗB (k 21cat). In addition, the system also showed considerable sensitivity to random changes in kinetic parameteres involved in transcriptional control.