Role of PA in Other Cellular Systems

PA derived from PC can be converted into DAG through the action of phospha-tidate phosphatase. It remains controversial whether DAG derived from this source can activate PKC. Initial studies indicated that treatment of fibroblasts with thrombin induced a rapid, transient phase of membrane translocation of PKCa fhat was correlated wifh transient rises in DAG and Ch due to IBP, breakdown [196]. In contrast, the membrane translocation of PKCe induced by thrombin persisted for at least an hour and was associated wifh a second prolonged phase of DAG accumulation [196]. Platelet-derived growth factor (PDGF) did not induce PKCa translocation, but caused a slow membrane association of PKCe which was 

Other studies have indicated that PG and PLD are a major source of PA in cells stimulated with various agonists [197-200] and several studies have confirmed biphasic formation of DAG, with the first phase derived from PIP2 and the second from PC via PA [201-205]. Analyses of the specific fatty acid composition of PA and PtdBut derived from cells treated with butanol and stimulated by bombesin or LPA also showed a predominance of saturated and mono-unsaturated fatty acids in the lipids derived from PLD action [206]. The fatty acid composition was very different from that found in DAG generated by PLC action on PIP2, in which polyunsaturated fatty acids predominate. The key issue is whether the DAG species derived from PC can activate PKC. Although studies indicate that this species is active on PKC in vitro, this has not been demonstrated in vivo. As described above [196], PC-derived DAG can activate Ca +-independent PKC isozymes but, because of the lack of a Ca rise, it cannot activate ( a -dcpcridcril PKC isozymes. 

It is probable that additional physiological targets of PA will be found, and that the full range of PLD actions in vivo is yet to be revealed. 

Interthal, J. J. PouLiOT, and J.J. Champoux, Proc. Natl. Acad. Sci. USA 

CoNRicoDE, J.L. Smith, D.J. Burns, and J.H. Exton, FEBS Lett., 

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