The Regulation of Lipid Signaling : Implications of Lipid-metabolizing Enzymes

Minor cellular lipids such as diacylglycerol, phosphatidic acid and lysophosphatidic acid are now established to act as lipid mediators regulating a wide range of cellular functions. To maintain orchestrated cellular functions, the concentration of such lipids needs to be strictly regulated by the balance of production and attenuation achieved by the action of metabolic enzymes. We are the first to report successful molecular cloning of two classes of enzymes, i. e. diacylglycerol kinase (DGK) and phosphatidic acid phosphatase (PAP). DGK has been disclosed to be involved in the attenuation of diacylglycerol-signal occurring within spatio-temporally regulated signaling complexes. PAP, on the other hand, acts as an ecto-enzyme degrading extracellular lipid signals like lysophosphatidic acid and sphingosine-1-phosphate, thus resulting in the attenuation of cell surface receptor-mediated lipid signaling. This review summarizes our recent work on the implications of DGK and PAP