Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
1-phosphatidylinositol-5-phosphate 4-kinase activity
Functional analysis of the biochemical activity of mammalian phosphatidylinositol 5 phosphate 4-kinase enzymes.
Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) are enzymes that catalyse the phosphorylation of phosphatidylinositol 5-phosphate (PI5P) to generate PI(4,5)P<sub>2</sub> Mammalian genomes contain three genes, <i>PIP4K2Α, 2B</i> and <i>2C</i> and murine knockouts for these suggested important physiological roles <i>in vivo</i> The proteins encoded by <i>PIP4K2A, 2B</i> and <i>2C</i> show widely varying specific activities <i>in vitro</i>; PIP4K2A is highly active and PIP4K2C 2000-times less active, and the relationship between this biochemical activity and <i>in vivo</i> function is unknown. By contrast, the <i>Drosophila</i> genome encodes a single PIP4K (dPIP4K) that shows high specific activity <i>in vitro</i> and loss of this enzyme results in reduced salivary gland cell size <i>in vivo</i> We find that the kinase activity of dPIP4K is essential for normal salivary gland cell size <i>in vivo</i> Despite their highly divergent specific activity, we find that all three mammalian PIP4K isoforms are able to enhance salivary gland cell size in the <i>Drosophila</i> PIP4K null mutant implying a lack of correlation between <i>in vitro</i> activity measurements and <i>in vivo</i> function. Further, the kinase activity of PIP4K2C, reported to be almost inactive <i>in vitro</i>, is required for <i>in vivo</i> function. Our findings suggest the existence of unidentified factors that regulate PIP4K enzyme activity <i>in vivo</i>.