Phosphoinositide fatty acids regulate phosphatidylinositol 5-kinase, phospholipase C and protein kinase C activities.
PtdIns(4,5)P(2) generally results from phosphorylation of PtdIns(4)P by the phosphatidylinositol 5-kinase (PtdIns5-K). Its hydrolysis by phospholipase C (PLC) yields inositol 1,4,5-trisphosphate and diacylglycerol, which stimulates protein kinase C (PKC). We show that epithelial cells of the cockroach rectum contain three different inositol lipids: PtdIns(4,5)P(2), PtdIns(4)P, and PtdIns. They are composed of six major fatty acids: palmitic (16:0) stearic (18:0), oleic (18:1n--9), linoleic (18:2n--6), linolenic (18:3n--3), and arachidonic (20:4n-6) acids. The fatty acid preference of each of the above enzymes was evaluated by incorporating different fatty acids in pairs into membrane lipids. Incorporation of 16:0 plus 18:1n--9 provoked an increase in PtdIns(4,5)P2-PLC activity and a decrease in PtdIns5-K activity. In contrast, incorporation of 16:0 plus 18:3n--3 led to a potentiation of PtdIns5-K activity and a decrease in PtdIns(4,5)P(2)-PLC activity. Furthermore, PLC and PtdIns5-K acted preferentially on substrates containing 18:3n--3, and 18:3n--3-containing diacylglycerol specifically potentiated PKC activity. Thus, we propose that the fatty acids that make up the phosphoinositides function as intracellular modulators of the activity of certain enzymes.
UMR 5017 CNRS, Laboratoire de Physiopathologie et Pharmacologie Vasculaire, Université Victor Segalen Bordeaux II, France.
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Carricaburu
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Fournier
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003058:Cockroaches / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D004075:Diglycerides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D007301:Insect Hormones / Q000494:pharmacology; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012007:Rectum / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D005227:Fatty Acids; D007301:Insect Hormones; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; C058919:neuroparsin A; C037178:phosphatidylinositol 4-phosphate; D015240:Phorbol 12,13-Dibutyrate; C095504:FAB1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium