Molecular mechanisms for regulation and physiological role of phospholipase D

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It has been known that phospholipase D (PLD) has been implicated in a variety of signal transduction pathways, including secretion, vesicle trafficking, mitosis and meiosis. However, the physiological role of PLD in cell functions has not yet been elucidated. In this research project, we have investigated the role of PLD in various cell functions, such as cell growth, differentiation and apoptosis. We have cloned three PLD genes (rPLD1a, 1b, 2) from rat P012 cell and their chromosome mapping were performed by fluorescent in situ hybridization (FISH). The levels of mRNA of PLD isozymes (rPLD1a, 1b, 2) were examined in the course of the apoptotic process induced by C2-ceramide in rat basophilic leukemia RBL cells and glioma C6 cells. The mRNA levels of PLD1a, and PLD1b were greatly decreased whereas the level of PLD2 was in contrast increased. Two forms of PLD (ARF- and oleate-dependent PLDs) have been found to be present in nuclei isolated from rat hepatocytes The ADP-ribosylation factor (ARF)-dependent PLD, but not oleate-dependent PLD activity was increased in the S-phase of the regenerating rat liver after partial hepatectomy, suggesting that the nuclear ARF-dependent PLD may be associated with cell proliferation. The oleate-dependent PLD activity was abundantly present in rat P012 cells, which may be regulated by mitogen-activated protein kinase stimulated by [1202. The oleate-dependent PLD activity also was increased during Actinomycine D-induced Jurkat T cell apoptosis. These results suggest that distinct PLD isozymes may be involved in different cell functions.