Phosphorylation/inactivation of PTEN by Akt-independent PI3K signaling in retinal pigment epithelium

► We decipher intracellular signaling pathways that induce the phosphorylation/inactivation of PTEN. ► Elevated reactive oxygen species (ROS) in AMD model mouse RPE trigger PTEN phosphorylation. ► The ROS-induced PTEN phosphorylation was not mediated by either GSK3 or CKII, two known PTEN kinases. ► The Akt-independent PI3K signaling pathway is responsible for PTEN phosphorylation in oxidatively damaged RPE.