Possible role of phospholipase D in cellular differentiation and apoptosis.
Phospholipase D (PLD) is widely distributed in mammalian cells and is implicated in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipases. Recently, two related PLD isozymes, PLD1 and PLD2, were cloned. The former activity is regulated in vitro by protein kinase C and small molecular weight GTP-binding proteins (Arf and Rho family). By contrast, the basal activity of the latter is high and it is unresponsive in vitro to these activators. The cellular PLD activity and mRNA levels of these PLD isozymes drastically changed during differentiation and apoptosis in several types of cells. The general trend was that the mRNA level of PLD1 increased during differentiation, as did the observed GTP gamma S-dependent PLD activity which presumably derived from PLD1-specific catalysis. In contrast, the PLD activity and mRNA level of PLD1 were down-regulated during apoptosis. In addition to these PLD isozymes, there exists another PLD isozyme which is activated by unsaturated fatty acids such as oleic acid, although its molecular nature and physiological roles are not well defined. We have observed that this type of PLD activity is drastically increased during apoptosis of Jurkat T cells, which mainly possess this kind of PLD activity. These results suggest the possibility that PLD activity is controlled at the transcriptional level in certain circumstances, and that PLD plays roles in differentiation, survival and apoptosis in mammalian cells.
Nakashima
S
S
Department of Biochemistry, Gifu University School of Medicine, Japan.
Nozawa
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008322:Mammals; D010739:Phospholipase D / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
D007527:Isoenzymes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011494:Protein Kinases; D010739:Phospholipase D; D019204:GTP-Binding Proteins