Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes

The importance of phosphoinositides as lipid signaling molecules in eucaryotic cells was first recognized by Lowell and Mabel Hokin in the 1950s (who also discovered the enzyme activities that phosphorylate phosphatidylinositol (PI)1). Since those early years, PI signaling pathways have expanded both in importance and complexity. The classical pathway transforms PI to PI-4,5-P2 by the successive actions of PI 4-kinases and PI-4-P 5-kinases. PI-4,5-P2 is the precursor for second messengers and also acts directly to modify effectors, for example actin-binding proteins. Significant roles for other phosphoinositide lipid products in signaling, combined with recently identified lipid kinase activities, are illuminating the many mechanisms by which cells use lipid messengers. This review will focus on the phosphatidylinositol-phosphate kinase (PIPK) family, which has the ability to synthesize all known PIP2 isomers and PIP3.