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Inhibition of phosphatidic acid phosphohydrolase activity by sphingosine
Author(s) -
Lavie Yaakov,
Piterman Orly,
Liscovitch Mordechai
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80796-l
Subject(s) - phosphatidic acid , sphingosine , chemistry , biochemistry , phospholipid , membrane , receptor
Recent evidence indicates that a major fraction of diacylglycerol that is produced in hormonally stimulated cells arises by phosphatidylcholine hydrolysis via the sequential action of phospholipase D and phosphatidic acid phosphohydrolase (PAP). We have previously reported that sphingoid bases stimulate phospholipase D activity in NG108‐15 cells. The evidence presented here demonstrates that in sphingosine‐treated NG108‐15 cells, elevated phosphatidic acid levels are accompanied by a parallel, time‐ and dose‐dependent decrease in diacylglycerol levels. DL‐propranolol, a known inhibitor of PAP, exerted similar effects, suggesting that the action of sphingosine may have been due to inhibition of PAP activity. This prediction was confirmed in in vitro experiments in which it was demonstrated that sphingosine is as potent an inhibitor of both cytosolic and membrane‐associated PAP activity as propranolol. The hypothesis that sphingoid bases may exert a dual action in diacylglycerol signal termination is proposed.