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. 1987 Dec 15;248(3):791–799. doi: 10.1042/bj2480791

Guanine-nucleotide and hormone regulation of polyphosphoinositide phospholipase C activity of rat liver plasma membranes. Bivalent-cation and phospholipid requirements.

S J Taylor 1, J H Exton 1
PMCID: PMC1148619  PMID: 2829842

Abstract

The effect of the GTP analogue guanosine 5'-[gamma-thio]triphosphate (GTP[S]) on the polyphosphoinositide phospholipase C (PLC) of rat liver was examined by using exogenous [3H]phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. GTP[S] stimulated the membrane-bound PLC up to 20-fold, with a half-maximal effect at approx. 100 nM. Stimulation was also observed with guanosine 5'-[beta gamma-imido]triphosphate, but not with adenosine 5'-[gamma-thio]triphosphate, and was inhibited by guanosine 5'-[beta-thio]diphosphate. Membrane-bound PLC was entirely Ca2+-dependent, and GTP[S] produced both a decrease in the Ca2+ requirement and an increase in activity at saturating [Ca2+]. The stimulatory action of GTP[S] required millimolar Mg2+. [8-arginine]Vasopressin (100 nM) stimulated the PLC activity approx. 2-fold in the presence of 10 nM-GTP[S], but had no effect in the absence of GTP[S] or at 1 microM-GTP[S]. The hydrolysis of PtdIns(4,5)P2 by membrane-bound PLC was increased when the substrate was mixed with phosphatidylethanolamine, phosphatidylcholine or various combinations of these with phosphatidylserine. With PtdIns(4,5)P2, alone or mixed with phosphatidylcholine, GTP[S] evoked little or no stimulation of the PLC activity. However, maximal stimulation by GTP[S] was observed in the presence of a 2-fold molar excess of phosphatidylserine or various combinations of phosphatidylethanolamine and phosphatidylserine. Hydrolysis of [3H]phosphatidylinositol 4-phosphate by membrane-bound PLC was also increased by GTP[S]. However, [3H]phosphatidylinositol was a poor substrate, and its hydrolysis was barely affected by GTP[S]. Cytosolic PtdIns(4,5)P2-PLC exhibited a Ca2+-dependence similar to that of the membrane-bound activity, but was unaffected by GTP[S]. It is concluded that rat liver plasma membranes possess a Ca2+-dependent polyphosphoinositide PLC that is activated by hormones and GTP analogues, depending on the Mg2+ concentration and phospholipid environment. It is proposed that GTP analogues and hormones, acting through a guanine nucleotide-binding protein, activate the enzyme mainly by lowering its Ca2+ requirement.

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Selected References

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  1. Baldassare J. J., Fisher G. J. Regulation of membrane-associated and cytosolic phospholipase C activities in human platelets by guanosine triphosphate. J Biol Chem. 1986 Sep 15;261(26):11942–11944. [PubMed] [Google Scholar]
  2. Banno Y., Nakashima S., Nozawa Y. Partial purification of phosphoinositide phospholipase C from human platelet cytosol; characterization of its three forms. Biochem Biophys Res Commun. 1986 Apr 29;136(2):713–721. doi: 10.1016/0006-291x(86)90498-5. [DOI] [PubMed] [Google Scholar]
  3. Bell R. M. Protein kinase C activation by diacylglycerol second messengers. Cell. 1986 Jun 6;45(5):631–632. doi: 10.1016/0092-8674(86)90774-9. [DOI] [PubMed] [Google Scholar]
  4. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J. 1983 Jun 15;212(3):849–858. doi: 10.1042/bj2120849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blackmore P. F., Exton J. H. Studies on the hepatic calcium-mobilizing activity of aluminum fluoride and glucagon. Modulation by cAMP and phorbol myristate acetate. J Biol Chem. 1986 Aug 25;261(24):11056–11063. [PubMed] [Google Scholar]
  7. Bradford P. G., Rubin R. P. Guanine nucleotide regulation of phospholipase C activity in permeabilized rabbit neutrophils. Inhibition by pertussis toxin and sensitization to submicromolar calcium concentrations. Biochem J. 1986 Oct 1;239(1):97–102. doi: 10.1042/bj2390097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brass L. F., Laposata M., Banga H. S., Rittenhouse S. E. Regulation of the phosphoinositide hydrolysis pathway in thrombin-stimulated platelets by a pertussis toxin-sensitive guanine nucleotide-binding protein. Evaluation of its contribution to platelet activation and comparisons with the adenylate cyclase inhibitory protein, Gi. J Biol Chem. 1986 Dec 25;261(36):16838–16847. [PubMed] [Google Scholar]
  9. Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
  10. Cockcroft S. The dependence on Ca2+ of the guanine-nucleotide-activated polyphosphoinositide phosphodiesterase in neutrophil plasma membranes. Biochem J. 1986 Dec 1;240(2):503–507. doi: 10.1042/bj2400503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Deckmyn H., Tu S. M., Majerus P. W. Guanine nucleotides stimulate soluble phosphoinositide-specific phospholipase C in the absence of membranes. J Biol Chem. 1986 Dec 15;261(35):16553–16558. [PubMed] [Google Scholar]
  12. Exton J. H. Mechanisms involved in calcium-mobilizing agonist responses. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1986;20:211–262. [PubMed] [Google Scholar]
  13. Gilman A. G. Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase. J Clin Invest. 1984 Jan;73(1):1–4. doi: 10.1172/JCI111179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gonzales R. A., Crews F. T. Guanine nucleotides stimulate production of inositol trisphosphate in rat cortical membranes. Biochem J. 1985 Dec 15;232(3):799–804. doi: 10.1042/bj2320799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hofmann S. L., Majerus P. W. Modulation of phosphatidylinositol-specific phospholipase C activity by phospholipid interactions, diglycerides, and calcium ions. J Biol Chem. 1982 Dec 10;257(23):14359–14364. [PubMed] [Google Scholar]
  16. Irvine R. F., Letcher A. J., Dawson R. M. Phosphatidylinositol-4,5-bisphosphate phosphodiesterase and phosphomonoesterase activities of rat brain. Some properties and possible control mechanisms. Biochem J. 1984 Feb 15;218(1):177–185. doi: 10.1042/bj2180177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jackowski S., Rettenmier C. W., Sherr C. J., Rock C. O. A guanine nucleotide-dependent phosphatidylinositol 4,5-diphosphate phospholipase C in cells transformed by the v-fms and v-fes oncogenes. J Biol Chem. 1986 Apr 15;261(11):4978–4985. [PubMed] [Google Scholar]
  18. Kaibuchi K., Takai Y., Nishizuka Y. Cooperative roles of various membrane phospholipids in the activation of calcium-activated, phospholipid-dependent protein kinase. J Biol Chem. 1981 Jul 25;256(14):7146–7149. [PubMed] [Google Scholar]
  19. Kamisaka Y., Toyoshima S., Osawa T. Phosphatidylinositol-specific phospholipase C of murine lymphocytes. Arch Biochem Biophys. 1986 Sep;249(2):569–578. doi: 10.1016/0003-9861(86)90035-4. [DOI] [PubMed] [Google Scholar]
  20. Litosch I., Fain J. N. 5-Methyltryptamine stimulates phospholipase C-mediated breakdown of exogenous phosphoinositides by blowfly salivary gland membranes. J Biol Chem. 1985 Dec 25;260(30):16052–16055. [PubMed] [Google Scholar]
  21. Litosch I., Wallis C., Fain J. N. 5-Hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands. Evidence for a role of GTP in coupling receptor activation to phosphoinositide breakdown. J Biol Chem. 1985 May 10;260(9):5464–5471. [PubMed] [Google Scholar]
  22. Low M. G., Carroll R. C., Cox A. C. Characterization of multiple forms of phosphoinositide-specific phospholipase C purified from human platelets. Biochem J. 1986 Jul 1;237(1):139–145. doi: 10.1042/bj2370139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lynch C. J., Blackmore P. F., Charest R., Exton J. H. The relationships between receptor binding capacity for norepinephrine, angiotensin II, and vasopressin and release of inositol trisphosphate, Ca2+ mobilization, and phosphorylase activation in rat liver. Mol Pharmacol. 1985 Aug;28(2):93–99. [PubMed] [Google Scholar]
  24. Magnaldo I., Talwar H., Anderson W. B., Pouysségur J. Evidence for a GTP-binding protein coupling thrombin receptor to PIP2-phospholipase C in membranes of hamster fibroblasts. FEBS Lett. 1987 Jan 1;210(1):6–10. doi: 10.1016/0014-5793(87)81287-5. [DOI] [PubMed] [Google Scholar]
  25. Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
  26. Martin T. F., Lucas D. O., Bajjalieh S. M., Kowalchyk J. A. Thyrotropin-releasing hormone activates a Ca2+-dependent polyphosphoinositide phosphodiesterase in permeable GH3 cells. GTP gamma S potentiation by a cholera and pertussis toxin-insensitive mechanism. J Biol Chem. 1986 Feb 25;261(6):2918–2927. [PubMed] [Google Scholar]
  27. Melin P. M., Sundler R., Jergil B. Phospholipase C in rat liver plasma membranes. Phosphoinositide specificity and regulation by guanine nucleotides and calcium. FEBS Lett. 1986 Mar 17;198(1):85–88. doi: 10.1016/0014-5793(86)81189-9. [DOI] [PubMed] [Google Scholar]
  28. Nakanishi H., Nomura H., Kikkawa U., Kishimoto A., Nishizuka Y. Rat brain and liver soluble phospholipase C: resolution of two forms with different requirements for calcium. Biochem Biophys Res Commun. 1985 Oct 30;132(2):582–590. doi: 10.1016/0006-291x(85)91173-8. [DOI] [PubMed] [Google Scholar]
  29. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  30. Orellana S., Solski P. A., Brown J. H. Guanosine 5'-O-(thiotriphosphate)-dependent inositol trisphosphate formation in membranes is inhibited by phorbol ester and protein kinase C. J Biol Chem. 1987 Feb 5;262(4):1638–1643. [PubMed] [Google Scholar]
  31. Prpić V., Green K. C., Blackmore P. F., Exton J. H. Vasopressin-, angiotensin II-, and alpha 1-adrenergic-induced inhibition of Ca2+ transport by rat liver plasma membrane vesicles. J Biol Chem. 1984 Feb 10;259(3):1382–1385. [PubMed] [Google Scholar]
  32. Rock C. O., Jackowski S. Thrombin- and nucleotide-activated phosphatidylinositol 4,5-bisphosphate phospholipase C in human platelet membranes. J Biol Chem. 1987 Apr 25;262(12):5492–5498. [PubMed] [Google Scholar]
  33. Ryu S. H., Cho K. S., Lee K. Y., Suh P. G., Rhee S. G. Two forms of phosphatidylinositol-specific phospholipase C from bovine brain. Biochem Biophys Res Commun. 1986 Nov 26;141(1):137–144. doi: 10.1016/s0006-291x(86)80345-x. [DOI] [PubMed] [Google Scholar]
  34. Sasaguri T., Hirata M., Kuriyama H. Dependence on Ca2+ of the activities of phosphatidylinositol 4,5-bisphosphate phosphodiesterase and inositol 1,4,5-trisphosphate phosphatase in smooth muscles of the porcine coronary artery. Biochem J. 1985 Nov 1;231(3):497–503. doi: 10.1042/bj2310497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schacht J. Purification of polyphosphoinositides by chromatography on immobilized neomycin. J Lipid Res. 1978 Nov;19(8):1063–1067. [PubMed] [Google Scholar]
  36. Smith C. D., Lane B. C., Kusaka I., Verghese M. W., Snyderman R. Chemoattractant receptor-induced hydrolysis of phosphatidylinositol 4,5-bisphosphate in human polymorphonuclear leukocyte membranes. Requirement for a guanine nucleotide regulatory protein. J Biol Chem. 1985 May 25;260(10):5875–5878. [PubMed] [Google Scholar]
  37. Straub R. E., Gershengorn M. C. Thyrotropin-releasing hormone and GTP activate inositol trisphosphate formation in membranes isolated from rat pituitary cells. J Biol Chem. 1986 Feb 25;261(6):2712–2717. [PubMed] [Google Scholar]
  38. Takenawa T., Nagai Y. Purification of phosphatidylinositol-specific phospholipase C from rat liver. J Biol Chem. 1981 Jul 10;256(13):6769–6775. [PubMed] [Google Scholar]
  39. Uhing R. J., Prpic V., Jiang H., Exton J. H. Hormone-stimulated polyphosphoinositide breakdown in rat liver plasma membranes. Roles of guanine nucleotides and calcium. J Biol Chem. 1986 Feb 15;261(5):2140–2146. [PubMed] [Google Scholar]
  40. Wallace M. A., Fain J. N. Guanosine 5'-O-thiotriphosphate stimulates phospholipase C activity in plasma membranes of rat hepatocytes. J Biol Chem. 1985 Aug 15;260(17):9527–9530. [PubMed] [Google Scholar]
  41. Wang P., Toyoshima S., Osawa T. Partial purification and characterization of membrane-bound and cytosolic phosphatidylinositol-specific phospholipases C from murine thymocytes. J Biochem. 1986 Oct;100(4):1015–1022. doi: 10.1093/oxfordjournals.jbchem.a121780. [DOI] [PubMed] [Google Scholar]
  42. Wilson D. B., Bross T. E., Hofmann S. L., Majerus P. W. Hydrolysis of polyphosphoinositides by purified sheep seminal vesicle phospholipase C enzymes. J Biol Chem. 1984 Oct 10;259(19):11718–11724. [PubMed] [Google Scholar]

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