Interaction of extracellular-signal molecules with cell-surface receptors often activates a phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine and other phospholipids, generating phosphatidic acid. The activation of PLD is believed to play an important role in the regulation of cell function and cell fate. Multiple PLD activities were characterized in eukaryotic cells, and, more recently, several PLD genes have been cloned. A PLD gene superfamily, defined by a number of structural domains and sequence motifs, also includes phosphatidyltransferases and certain phosphodiesterases. Among the eukaryotic PLD genes are those from mammals, nematodes, fungi and plants. The present review focuses on the structure, localization, regulation and possible functions of cloned mammalian and yeast PLDs. In addition, an overview of plant PLD genes, and of several distinct PLD activities that have not yet been cloned, is provided. Emerging evidence from recent work employing new molecular tools indicates that different PLD isoforms are localized in distinct cellular organelles, where they are likely to serve diverse functions in signal transduction, membrane vesicle trafficking and cytoskeletal dynamics.

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Interaction of extracellular-signal molecules with cell-surface receptors often activates a phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine and other phospholipids, generating phosphatidic acid. The activation of PLD is believed to play an important role in the regulation of cell function and cell fate. Multiple PLD activities were characterized in eukaryotic cells, and, more recently, several PLD genes have been cloned. A PLD gene superfamily, defined by a number of structural domains and sequence motifs, also includes phosphatidyltransferases and certain phosphodiesterases. Among the eukaryotic PLD genes are those from mammals, nematodes, fungi and plants. The present review focuses on the structure, localization, regulation and possible functions of cloned mammalian and yeast PLDs. In addition, an overview of plant PLD genes, and of several distinct PLD activities that have not yet been cloned, is provided. Emerging evidence from recent work employing new molecular tools indicates that different PLD isoforms are localized in distinct cellular organelles, where they are likely to serve diverse functions in signal transduction, membrane vesicle trafficking and cytoskeletal dynamics.

We have previously reported the identification and partial characterization of a gene encoding a phospholipase D activity (PLD1) in the yeast, Saccharomyces cerevisiae. Here we report the existence of a second phospholipase D activity, designated PLD2, in yeast cells bearing disruption at the PLD1 locus. PLD2 is a Ca 2؉ -dependent enzyme which preferentially utilizes phosphatidylethanolamine over phosphatidylcholine as a substrate. In contrast to PLD1, the activity of PLD2 is insensitive to phosphatidylinositol 4,5-bisphosphate, and the enzyme is incapable of catalyzing the transphosphatidylation reaction with short chain alcohols as acceptors. Subcellular fractionation shows that PLD2 localizes mainly to the cytosol, but could also be detected in the particulate fraction. Thus, the biochemical properties of PLD2 appear to be substantially different from those of PLD1. PLD2 activity is significantly and transiently elevated upon exit of wild type yeast cells from stationary phase, suggesting that it may play a role in the initiation of mitotic cell division in yeast. In view of the significantly different properties of PLD1 and PLD2, and because the yeast genome contains PLD1 as the sole member of the recently defined PLD gene family, it may be concluded that PLD2 is structurally unrelated to PLD1. Thus, the novel PLD2 activity described herein is likely to represent the first identified member of a new PLD gene family.

. Upon engagement of chemoattractant receptors, neutrophils generate inositol trisphosphate and diacylglycerol (DG) by means of a phosphatidylinositolspecific phospholipase C (PI-PLC) which is regulated by a GTP-binding protein(s) . We have previously reported (Reibman, J., H. M. Korchak, L. B. Vosshall, K. A. Haines, A. M. Rich, and G. Weissmann. 1988. J. Biol. Chem. 263 :6322-6328) a biphasic rise in DG after exposure of neutrophils to the chemoattractant FMLP: a rapid (<15 s) phase ("triggering") and a slow (>,30 s) phase ("activation") . These derive from distinct intracellular lipid pools. To study the source of rapid and slow DG, we have used a unique probe, protein I, a porin that is the major outer membrane protein of Neisseria gonorrhoeae. Treatment of neutrophils with protein I inhibits exocytosis and homotypic cell adhesion provoked by FMLP without inhibiting assembly of the NADPH oxidase responsible for OZ genera-