The orchestrated signaling by PI3Kα and PTEN at the membrane interface

Danai Maria Kotzampasi; Kyriaki Premeti; Alexandra Papafotika; Vasiliki Syropoulou; Savvas Christoforidis; Zoe Cournia; George Leondaritis

doi:10.1016/j.csbj.2022.10.007

The orchestrated signaling by PI3Kα and PTEN at the membrane interface

Comput Struct Biotechnol J. 2022 Oct 7:20:5607-5621. doi: 10.1016/j.csbj.2022.10.007. eCollection 2022.

Authors

Danai Maria Kotzampasi^{1

2}, Kyriaki Premeti³, Alexandra Papafotika^{4

5}, Vasiliki Syropoulou³, Savvas Christoforidis^{4

5}, Zoe Cournia¹, George Leondaritis^{3

6}

Affiliations

¹ Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
² Department of Biology, University of Crete, Heraklion 71500, Greece.
³ Laboratory of Pharmacology, Faculty of Medicine, University of Ioannina, Ioannina 45110, Greece.
⁴ Laboratory of Biological Chemistry, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece.
⁵ Biomedical Research Institute, Foundation for Research and Technology, Ioannina 45110, Greece.
⁶ Institute of Biosciences, University Research Center of Ioannina, Ioannina 45110, Greece.

Abstract

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.

Keywords: Allostery; Membrane trafficking; Membrane-binding; PI3Kα; PTEN; Phosphoinositides.

Publication types

Review