FIG 4.

Activation of AMPK signaling induces K-Ras displacement from the PM. (A) The AMPK → PKG signaling pathway leading to K-Ras phosphorylation, with activators indicated in blue and inhibitors indicated in red. (B) MDCK cells stably coexpressing mGFP–K-RasG12V and mCherry-CAAX were treated with 0.5 μM oligomycin A, 100 μM 8-Br-cGMP, or 100 nM sildenafil in the presence (dotted line) or absence (solid line) of 1 mM l-NAME for 4 and 6 h. K-RasG12V PM dissociation was quantified using Manders coefficients from three independent experiments. Significant difference between drug-treated and control (vehicle-treated) cells were assessed using one-way ANOVA tests (N.S., not significant; **, P < 0.01; ***, P < 0.001).