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. Author manuscript; available in PMC: 2014 Dec 1.
Published in final edited form as: Mol Cancer Ther. 2013 Sep 27;12(12):10.1158/1535-7163.MCT-13-0439. doi: 10.1158/1535-7163.MCT-13-0439

Figure 5.

Figure 5

Proposed mechanism by which metformin causes translocation of activated K-Ras from the plasma membrane and promotes cell death. Previous studies have shown that metformin activates atypical PKC (PKCĪ¶) through an AMPK-, ERK-, and PDK1-dependent mechanism. PKCĪ¶ then phosphorylates the lysine rich tail of activated K-Ras, acting as an electrostatic switch that causes K-Ras to be repelled from the membrane. This phosphorylation also promotes association between oncogenic K-Ras and Bcl-XL on the mitochondrial outer membrane, inducing apoptosis.