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Figure 4 | Molecular Cancer

Figure 4

From: Molecular features in arsenic-induced lung tumors

Figure 4

Arsenic-mediated disruption of PI3K/AKT signaling pathway. Depending on the receptor, different proteins can bind to the phosphorylated tyrosine residue of the RTK to recruit PI3K to the plasma membrane. There, the activated PI3K can interact with phosphatidylinositol 4,5-bisphosphate (PIP2) on the inner side of the membrane, and catalyze its phosphorylation to phosphatidylinositol 3,4,5-triphosphate (PIP3). PIP3 activates the kinase AKT, which is capable of phosphorylating a number of target proteins in the cytoplasm and nucleus. Some of the direct targets of PI3K (light blue) and AKT (grey), and their consequences on cell fate are depicted. Arsenic targets sulfhydryl groups of PI3K kinases such as c-Src, also resulting in activation of the PI3K/AKT pathway. AsIII can also activate AKT independently of PI3K, both through STAT3 and/or induction of miR-190. PTEN is an inhibitor of the pathway that has been shown to be a target of arsenic in stem cells. Among other mechanisms, methylation patterns at the promoter region of the p53 gene have been shown to be modified by arsenic, resulting in silencing of this tumor suppressor.

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