Fig 2: Activation of ERK and p38 by AdV in mouse liver and spleen.Phospho-ERK (p-ERK1/2) and phospo-p38 (p-p38) were quantitated by Western blot using phospho-specific antibodies. A. Av1nBg, injected i.v. at 5×1012 vp/kg, induced a rapid phosphorylation of ERK in the mouse liver, with a peak appearing at 30 min. * = p<0.05 vs. 30 min buffer control mice (ANOVA, Holm-Sidak). B. HDAd2 significantly induced phosphorylation of ERK in the liver and spleen and p38 in the liver at 30 minutes, but ts1 did not. Data are normalized to the buffer control group. 5 mice/group. * = p<0.05 vs. buffer control mice (ANOVA, Holm-Sidak).

Fig 3: Effect of kinase inhibitors on the serum cytokine response in mice receiving HDAd2 or LPS.Mice were orally administered either 8 ml/kg buffer, 100 mg/kg of the MEK (ERK pathway) inhibitor PD0325901 or 40 mg/kg of the p38 inhibitor SB239063. Sixty minutes later mice were injected i.v. with 5×1012 vp/kg HDAd2 or i.p. with 500 µg/kg LPS. Serum was collected at either 2 hours (LPS) or six hours (HDAd2) and evaluated for cytokine levels. A. The cytokine response to LPS was unaltered by inhibition of the ERK pathway with the exception of IP-10, which was signficantly elevated (left panel). In contrast, inhibition of the p38 pathway significantly reduced the response to LPS for all the tested chemokines/cytokines except KC (right panel). B. Inhibition of the ERK pathway altered the cytokine/chemokine response to HDAd2 (left panel), significantly inhibiting the serum levels of TNFα and KC and significantly elevating the expression of IL-12p70, IFNγ, IP-10 and IL-6. Pretreatment with the p38 inhibitor (right panel) significantly decreased the serum levels of IFNγ, IL-10 and IL-1β. The buffer controls were 0.5% methylcellulose and 0.5% acidified tragacanth for the ERK and p38 inhibitors, respectively. 3–5 mice/group, * = p<0.05 vs. corresponding buffer control (t-test).

Fig 4: Dual targeting of FRS2 and FRS3 is a global inhibitor of FGF induction. A and B: Migration experiments in PC3 and DU145 stimulated with different FGFs. C and D: Invasion assays for PC3 and DU145 cancer prostate cell lines in the presence of different FGFS and EGF. E: Silencing FRS2 and FRS3 inhibits FGF-simulated ERK activation of PC3 cells by FGF1 and FGF2 (*p < 0.005). siFRS2/3- siRNA against FRS2 and FRS3