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Review
. 2018 May;68:31-38.
doi: 10.1016/j.jbior.2018.02.003. Epub 2018 Feb 8.

Phosphoinositide 3-kinase Pathways and Autophagy Require Phosphatidylinositol Phosphate Kinases

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Free PMC article
Review

Phosphoinositide 3-kinase Pathways and Autophagy Require Phosphatidylinositol Phosphate Kinases

Suyong Choi et al. Adv Biol Regul. .
Free PMC article

Abstract

Phosphatidylinositol phosphate kinases (PIPKs) generate a lipid messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2) that controls essentially all aspects of cellular functions. PI4,5P2 rapidly diffuses in the membrane of the lipid bilayer and does not greatly change in membrane or cellular content, and thus PI4,5P2 generation by PIPKs is tightly linked to its usage in subcellular compartments. Based on this verity, recent study of PI4,5P2 signal transduction has been focused on investigations of individual PIPKs and their underlying molecular regulation of cellular processes. Here, we will discuss recent advances in the study of how PIPKs control specific cellular events through assembly and regulation of PI4,5P2 effectors that mediate specific cellular processes. A focus will be on the roles of PIPKs in control of the phosphoinositide 3-kinase pathway and autophagy.

Keywords: Autophagy; Phosphatidylinositol 4,5-bisphosphate; Phosphatidylinositol phosphate kinase; Phosphoinositide; Phosphoinositide 3-kinase; Signal transduction.

Conflict of interest statement

The authors have declared no conflict of interest.

Figures

Figure 1
Figure 1
A schematic representation of PI4,5P2 generation by type I vs. type II PIP kinases. Type I PIP kinase isoforms phosphorylate the 5’ hydroxyl group of the insositol ring, while type II enzymes phosphorylate the 4’ hydroxyl group. Once PI4,5P2 is generated, it binds to a set of protein targets called PI4,5P2 effectors and controls their activity, subcellular location, and PI4,5P2 effectors’ interaction with other proteins.
Figure 2
Figure 2
A schematic representation of the IQGAP1-scaffolded class I PI3K-Akt signaling platform. IQGAP1 binds to PI4KIIIα, PIPKIα, and class I PI3K that generate PI4P, PI4,5P2, and PI3,4,5P3, respectively. The generated PI3,4,5P3 is directly transferred to PDK1 and Akt, which are also associated with IQGAP1. In the IQGAP1-mediated multi-kinase complex, PI3,4,5P3 generation is tightly linked to its usage.
Figure 3
Figure 3
A schematic representation of the role of PIPK isoforms in autophagy. Each PIPK isoform has unique but sometimes redundant roles in the steps of autophagy progression. PIPKs and their product PI4,5P2 now have clear functional roles in autophagy generally by promoting membrane reformation.

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