Figure 2.

Regulation of PI3K/AKT signaling by N‐myc downstream‐regulated gene 2 (NDRG2)/protein phosphatase 2A (PP2A) complex. In normal cells, NDRG2 recruits PP2A to phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which induces the dephosphorylation of PTEN at Ser380/Thr382/Thr383 (PTEN‐STT cluster). This dephosphorylation of the PTEN‐STT cluster leads to the open conformation of the C‐tail that allows PTEN to associate with the cell membrane and the C2 domain can bind phosphatidylserine (PS) inside the cell membrane and the subsequent suppression of PI3K/AKT signaling via dephosphorylation of phosphatidylinositol 3,4,5‐trisphosphate (PIP3). In tumor cells, the loss of NDRG2 expression induces constitutive phosphorylation of the PTEN‐STT cluster, which prevents binding of PTEN to the cell membrane by the closed conformation, leading to constitutive AKT activation via inactivation of the phosphatase activity of PTEN. ⁶ This figure has been adapted from reference 6 with permission