Regulation of PTEN function as a PIP3 gatekeeper through membrane interaction

PTEN, one of the most frequently mutated genes in human cancer, acts as a tumor suppressor by dephosphorylating the plasma membrane lipid second messenger phosphoinositide-3,4,5-trisphosphate (PIP3) generated by the action of PI3Kinases. PTEN activity to prevent elevated levels of PIP3 and tumorigenesis depends on its interaction with the lipid bilayer. PTEN binds dynamically to the plasma membrane through a complex mix of protein-lipid and protein-protein interactions and the translocation is regulated by several mechanisms including C-terminal tail phosphorylations. Here we have summarized our current view of the interaction of PTEN with the plasma membrane and what the implications are for cancer biology.