Identification of Potential Pathway Mediation Targets in Toll-like Receptor Signaling
Figure 5
A simplified illustration of the reactive oxygen species (ROS) production DIOS pathway.
The three critical network reactions are highlighted in red. Although there were over forty reactions in the ROS production pathway, most were associated with the TLR-induced activation of various phox proteins by the protein kinases PDK1 and PKCz. However, because PDK1 and PKCz work in parallel, none of these reactions could control the flux through the entire pathway, and therefore were not critical network reactions. On the other hand, the three critical network reactions Vav1-Rac1/GDP binding, Rac1 phosphorylation, and gp91-p22 binding, produced the two other components that comprised the final phox protein complex, and were therefore critical to the overall output ROS production. Note also that these critical network reactions were localized to the ROS production pathway and did not interfere with other cellular processes. Thus, they represent ideal targets for mediation of TLR-induced ROS production.