Phosphoinositide 3-kinase (PI3K) classes: From cell signaling to endocytic recycling and autophagy

Lipid signaling is defined as any biological signaling action in which a lipid messenger binds to a protein target, converting its effects to specific cellular responses. In this complex biological pathway, the family of phosphoinositide 3-kinase (PI3K) represents a pivotal role and affects many aspects of cellular biology from cell survival, proliferation, and migration to endocytosis, intracellular trafficking, metabolism, and autophagy. While yeasts have a single isoform of phosphoinositide 3-kinase (PI3K), mammals possess eight PI3K types divided into three classes. The class I PI3Ks have set the stage to widen research interest in the field of cancer biology. The aberrant activation of class I PI3Ks has been identified in 30–50% of human tumors, and activating mutations in PIK3CA is one of the most frequent oncogenes in human cancer. In addition to indirect participation in cell signaling, class II and III PI3Ks primarily regulate vesicle trafficking. Class III PI3Ks are also responsible for autophagosome formation and autophagy flux. The current review aims to discuss the original data obtained from international research laboratories on the latest discoveries regarding PI3Ks-mediated cell biological processes. Also, we unravel the mechanisms by which pools of the same phosphoinositides (PIs) derived from different PI3K types act differently. •By transferring outer signals, class I PI3K participates in cell proliferation•Class II PI3K involves in vesicle trafficking and clathrin-mediated endocytosis•Vps34 (class III PI3K) induces the autophagosome and autolysosome formation•Nutrient regulation of mTORC1 through RAG GTPases was conducted by Vps34 complexes