Figure 1.

Cytoplasmic and nuclear PTEN signaling. In the cytoplasm, PTEN canonically functions to regulate the phosphatidylinositol 3-phosphate kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Under growth factor stimulation, PI3K is activated and catalyzes the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP₂) to phosphatidylinositol 3,4,5-triphosphate (PIP₃). PIP₃ recruits PDK1 to the plasma membrane, which then contributes to the activation of AKT. AKT regulates a myriad of downstream cellular processes such as cell growth, proliferation, and decreased apoptosis. The lipid phosphatase activity of PTEN counteracts PI3K by dephosphorylating PIP₃ to PIP₂, thereby dampening AKT activation. In the nucleus, PTEN plays a vital role in maintaining genomic stability, chromosomal architecture, cell-cycle control, and the regulation of ribosome biogenesis within nucleoli.