Phosphatidic acid: a lipid messenger involved in intracellular and extracellular signalling

Abstract

Generated during the initial phases of cell signalling, phosphatidic acid has been implicated as a messenger involved in the activation of cellular kinases and phospholipases as well as certain proto-oncogene products and low-molecular-weight G-proteins. Although many of the reported effects of phosphatidic acid can be attributed to metabolites generated by cellular hydrolases, the parent compound clearly possesses important biological activities. However, instead of acting as a ubiquitous second messenger mediating signalling events shared by a wide variety of cells, in many systems the phospholipid seems to function specifically, regulating unique functions confined to specialized groupings of cells. One such function is neutrophil superoxide generation, which is induced when phosphatidic acid, generated by activated phospholipase D (PLD), facilitates the interaction of a cytoplasmic low-molecular-weight G-protein with dormant, membrane-bound reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Positioned on the outer surface of the plasma membrane of triggering cells, phosphatidic acid potentially mediates the "juxtacrine" stimulation of cells in direct contact. This review critically evaluates the known biological effects of phosphatidic acid as opposed to functions induced by its metabolites and addresses the mechanisms by which these effects are specifically induced by this phospholipid.