The orchestrated signaling by PI3Kα and PTEN at the membrane interface

The oncogene PI3Kα and the tumor suppressor PTEN represent two antagonistic enzymatic activities that regulate the interconversion of the phosphoinositide lipids PI(4,5)P₂ and PI(3,4,5)P₃ in membranes. As such, they are defining components of phosphoinositide-based cellular signaling and membrane trafficking pathways that regulate cell survival, growth, and proliferation, and are often deregulated in cancer. In this review, we highlight aspects of PI3Kα and PTEN interplay at the intersection of signaling and membrane trafficking. We also discuss the mechanisms of PI3Kα- and PTEN- membrane interaction and catalytic activation, which are fundamental for our understanding of the structural and allosteric implications on signaling at the membrane interface and may aid current efforts in pharmacological targeting of these proteins.