Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in cells, organs, and animals: History and perspective

Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.