Figure 7

Loss of pEzrin on treatment with MK-2206 mediates cell death: A) Western blot analysis showing a reduction in the expression pEzrin (T567) on treatment with MK-2206 in vitro. B) Treatment with MK-2206 reduces the expression of pEzrin (T567) in vivo. Stable knockdown of Akt2 was performed in GEO cells. C) Western blot analysis showing a loss of pEzrin (T567) on knockdown of Akt2. No change in total Ezrin was observed on loss of Akt2. D) Western blot analysis showing loss of Akt1 does not affects the expression of pEzrin (T567). GAPDH is used as a loading control. E) Overall mechanism for induction of cell death by MK-2206. Akt kinase inhibitor MK-2206 mediates cell death by two different mechanisms. Loss of phosphorylation of Akt results in induction and translocation of AIF from the mitochondria to the nucleus, where it results in DNA fragmentation. On the other hand treatment with MK-2206 results in loss of pEzrin (T567), which results in loss of XIAP thus mediating cell death.