Regulation of phospholipase C delta activity by sphingomyelin and sphingosine.
Phospholipase C delta (PLC delta) is strongly inhibited by sphingomyelin (SM). The inhibition occurs in both the presence and the absence of spermine, an activator of PLC delta. Phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI) also inhibit PLC delta in the presence of spermine but are much less effective than SM. PE and PC activate and PS and PI inhibit PLC delta in the absence of spermine. Again, the inhibition by PS and PI is much weaker than the inhibition observed with SM. Similar or identical effects are observed in detergent micelle and liposome assays. Comparisons of physiological concentrations of SM with concentrations yielding 50% inhibition of PLC delta in vitro indicate that SM is likely to be a major factor in regulating the activity of PLC delta by inhibition. It is proposed that, in vivo, sphingomyelin acts as an inhibitor of PLC delta, which enables the enzyme to be regulated by activation. In certain circumstances, there is a substantial decline in SM and this may lead to a partial relief of the inhibition. PLC delta is activated by sphingosine in the absence of spermine. However, this activation occurs at unphysiologically high concentrations of sphingosine. The effects of SM and sphingosine on PLC delta in marked contrast to those observed with protein kinase C, which is unaffected by sphingomyelin and inhibited by sphingosine.
Pawelczyk
T
T
Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
Lowenstein
J M
JM
D000818:Animals; D004789:Enzyme Activation; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D015636:Magnesium Chloride / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D013096:Spermine / Q000494:pharmacology; D013109:Sphingomyelins / Q000494:pharmacology*; D013110:Sphingosine / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D007527:Isoenzymes; D008081:Liposomes; D010743:Phospholipids; D013109:Sphingomyelins; D015636:Magnesium Chloride; D013096:Spermine; D011189:Potassium Chloride; D010738:Type C Phospholipases; D013110:Sphingosine