Phosphoinositide fatty acids regulate phosphatidylinositol 5-kinase, phospholipase C and protein kinase C activities

Eur J Biochem. 2001 Mar;268(5):1238-49. doi: 10.1046/j.1432-1327.2001.01984.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cockroaches* / chemistry
  • Cockroaches* / enzymology
  • Cockroaches* / metabolism
  • Diglycerides / chemistry
  • Diglycerides / metabolism
  • Diglycerides / pharmacology
  • Enzyme Activation / drug effects
  • Epithelial Cells / chemistry
  • Epithelial Cells / enzymology
  • Epithelial Cells / metabolism
  • Fatty Acids / analysis
  • Fatty Acids / metabolism*
  • Insect Hormones / pharmacology
  • Microsomes / chemistry
  • Microsomes / metabolism
  • Phorbol 12,13-Dibutyrate / metabolism
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / pharmacology
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphatidylinositol Phosphates / pharmacology
  • Phosphatidylinositols / chemistry*
  • Phosphatidylinositols / metabolism*
  • Phosphatidylinositols / pharmacology
  • Phospholipids / analysis
  • Phospholipids / chemistry
  • Phospholipids / metabolism
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Kinase C / metabolism*
  • Rectum / chemistry
  • Rectum / enzymology
  • Rectum / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Type C Phospholipases / metabolism*

Substances

  • Diglycerides
  • Fatty Acids
  • Insect Hormones
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Phospholipids
  • Saccharomyces cerevisiae Proteins
  • neuroparsin A
  • phosphatidylinositol 4-phosphate
  • Phorbol 12,13-Dibutyrate
  • FAB1 protein, S cerevisiae
  • Phosphotransferases (Alcohol Group Acceptor)
  • Protein Kinase C
  • Type C Phospholipases
  • Calcium