FIGURE 7.
Effect of decoy mechanism on TRAIL signaling is negligible. A, relative distribution of TRAILR1 in three different receptor complexes as predicted by mathematical modeling for HeLa (expressing only TRAILR1; black), HeLa R4 (expressing TRAILR1 and TRAILR4 at comparable levels; blue), and HeLa R4+ cells (expressing ∼10-fold higher levels of TRAILR4 than TRAILR1; red) in the absence of ligand. B, dose response for the predicted proapoptotic activity of TRAIL, represented by the abundance of (TRAILR1)2-TRAIL complexes. C, dose response for the predicted proapoptotic activity of TRAIL, assuming that no receptor heterodimers are formed and that TRAILR4 merely inhibits apoptosis induction through a decoy mechanism. Lines showing relative receptor activation for the three cell lines are virtually identical and, therefore, indistinguishable. Bold lines represent the prediction for the parameter values stated under “Results.” Thin lines correspond to further parameter samples and are used to illustrate the effects of uncertainties in receptor-receptor interaction kinetics.