Phospholipase D: regulation and functional significance.

PLD is a major route for hydrolysis of PC 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. Little, however, is known at present about its enzymology and molecular biology. 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 will be the investigation of how products from the PLD pathway exert these effects. Current evidence suggests an important role for Ca(2+)-independent PKC isoforms and probably also for novel cellular targets for the putative second messenger PA.