The molecular mechanisms mediating class II PI 3‐kinase function in cell physiology

• Published in: The FEBS journal 2021-12, Vol.288 (24), p.7025-7042
• Main Authors: Koch, Philipp Alexander, Dornan, Gillian Leigh, Hessenberger, Manuel, Haucke, Volker
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Animals; cancer; Cell migration; Cell Movement; Cell signaling; endocytosis; Enzymatic activity; Enzymes; Humans; Insulin-Secreting Cells - metabolism; Kinases; Lipids; Localization; Membrane trafficking; Membranes; Molecular modelling; myopathy; nutrient signaling; Phosphatidylinositol 3-Kinases - metabolism; phosphatidylinositol 3‐kinase; Phosphoinositides; Physiology; Signal Transduction; Structure-function relationships; vesicle traffic
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.15692

The phosphoinositide 3‐kinase (PI3K) family of lipid‐modifying enzymes plays vital roles in cell signaling and membrane trafficking through the production of 3‐phosphorylated phosphoinositides. Numerous studies have analyzed the structure and function of class I and class III PI3Ks. In contrast, we know comparably little about the structure and physiological functions of the class II enzymes. Only recent studies have begun to unravel their roles in development, endocytic and endolysosomal membrane dynamics, signal transduction, and cell migration, while the mechanisms that control their localization and enzymatic activity remain largely unknown. Here, we summarize our current knowledge of the class II PI3Ks and outline open questions related to their structure, enzymatic activity, and their physiological and pathophysiological functions. Class II phosphatidylinositol 3‐kinases execute multiple functions in cellular processes ranging from signaling to membrane dynamics. Despite the numerous cell physiological roles of these enzymes, the precise molecular mechanisms that govern their localization and activity remain poorly understood. Here, we summarize our current knowledge of the class II PI3Ks and outline open questions related to their structure, enzymatic activity, and their physiological functions.