Phospholipid signaling: phosphoinositide kinases and phosphatases

Phosphoinositides are lipids that are present in the cytoplasmic leaflet of the plasma membrane and organelle membranes, and these play pivotal roles in the regulation of a wide variety of cellular processes. The site-specific phosphorylation and dephosphorylation of the hydroxyl groups of their inositol rings, controlled by a variety of phosphoinositide kinases and phosphoinositide phosphatases, result in the generation of the seven known phosphoinositide species, which have isomer-specific unique localization and functions. In mammals, nearly 50 genes encode the phosphoinositide kinases and phosphoinositide phosphatases that regulate phosphoinositide metabolism and thus allow cells to rapidly and effectively respond to environmental stimuli. The misregulation of phosphoinositide kinases and phosphatases is critical in human diseases, including cancer, immunodeficiencies, congenital disorders, and developmental disorders. This review summarizes the current knowledge of the biological properties of phosphoinositide kinases and phosphoinositide phosphatases, as well as their associations with human disorders.