Phospholipase D: Regulation and Functional Significance

This chapter discusses the evidence for the existence of receptor-coupled phospholipase D (PLD), together with recent information regarding its intracellular location, mode of activation, and functional role. PLD is a major route for hydrolysis of phosphatidylcholine in most tissues, consistent with it playing an important role in signal transduction. The enzyme appears to be activated by a variety of different mechanisms in different tissues, suggesting there might be several different isoforms. There is little direct evidence to indicate the functional significance of PLD activation but an accumulation of indirect evidence links PLD with prolonged changes in cell function. In particular, two areas where there is strong evidence for a role for PLD are mitogenesis and leukocyte hyperresponsiveness. An important area for future work can be the investigation of how products from the PLD pathway exert these effects. Current evidence suggests an important role for Ca 2+ -independent protein kinase C isoforms and probably also for novel cellular targets for the putative second messenger phosphatidic acid.