The orchestrated signaling by PI3K? and PTEN at the membrane interface

The oncogene PI3Ka 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 traffick-ing pathways that regulate cell survival, growth, and proliferation, and are often deregulated in cancer. In this review, we highlight aspects of PI3Ka and PTEN interplay at the intersection of signaling and mem-brane trafficking. We also discuss the mechanisms of PI3Ka- and PTEN-membrane interaction and cat-alytic 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 tar-geting of these proteins. CO 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Bio-technology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).