UCL Discovery

Abstract

The phosphatidylinositol 4-kinase (PI4K) class of enzyme activities is ubiquitous in eukaryotic cells and catalyses the phosphorylation of the membrane lipid phosphatidylinositol at the 4-OH position of the inositol residue, thereby generating phosphatidylinositol 4-monophosphate (PI(4)P). PI(4)P has important roles in signaling and intracellular membrane trafficking, most notably as a signaling precursor in phosphoinositide 3-kinase (PI3K) and phospholipase C pathways. However, it is also known that PI(4)P signals by recruiting cognate PH-domain-containing proteins involved in intracellular traffic, and the clathrin adaptors AP-1 and AP-3 to their target membranes. Such PI(4)P-protein interaction phenomena have only been described relatively recently and it is likely that many more direct targets of PI(4)P exist. The α and β isoforms (PI4KIIα and PI4KIIβ) that make up the type II PI4K family are structurally and biochemically distinct from type III PI4K enzymes, which are members of the PI3K family.