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.
Carricaburu
V
V
UMR 5017 CNRS, Laboratoire de Physiopathologie et Pharmacologie Vasculaire, Université Victor Segalen Bordeaux II, France.
Fournier
B
B
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