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 Mammalian genomes contain three genes, and and murine knockouts for these suggested important physiological roles The proteins encoded by and show widely varying specific activities ; PIP4K2A is highly active and PIP4K2C 2000-times less active, and the relationship between this biochemical activity and function is unknown. By contrast, the genome encodes a single PIP4K (dPIP4K) that shows high specific activity and loss of this enzyme results in reduced salivary gland cell size We find that the kinase activity of dPIP4K is essential for normal salivary gland cell size Despite their highly divergent specific activity, we find that all three mammalian PIP4K isoforms are able to enhance salivary gland cell size in the PIP4K null mutant implying a lack of correlation between activity measurements and function. Further, the kinase activity of PIP4K2C, reported to be almost inactive , is required for function. Our findings suggest the existence of unidentified factors that regulate PIP4K enzyme activity .