Fig. 3. PI3K and its downstream signal Akt are required for Met-triggered Mdm2 translation in embryonic hepatocytes. (A) Hgf-mediated Mdm2 induction and Akt phosphorylation in wild-type hepatocytes is inhibited by LY 294002 in a dose-dependent manner. (B) Western blot analysis showing that Akt siRNA causes a reduction in Mdm2 protein levels in a concentration-dependent manner (100 and 200 pmol). Levels of phospho-S₄₇₃ Akt and Akt, but not ERKs, were reduced in the presence of Akt siRNA. Control siRNA did not alter protein levels. (C) Hgf-induced Mdm2 translation is prevented by the Akt inhibitor A-443654 in a dose-dependent manner. Inhibition of Akt by A-443654 was confirmed following GSK3 phosphorylation.