Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1984 Aug 1;221(3):675–684. doi: 10.1042/bj2210675

Calcium signals and phospholipid methylation in eukaryotic cells.

J P Moore, A Johannsson, T R Hesketh, G A Smith, J C Metcalfe
PMCID: PMC1144097  PMID: 6477493

Abstract

Rat basophil leukaemic (2H3) cells, mast cells and mouse thymocytes respond to stimulation by specific ligands with an increase in the free cytosolic Ca2+ concentration. The time courses of these Ca signals and the biological responses have been compared with changes in phospholipid metabolism. Increased phosphoinositide metabolism coincides with the Ca signals and the responses in each cell system, whereas any increase in phospholipid methylation during the response is less than one molecule per receptor and at least 5-50-fold less than the increases reported previously. Furthermore, no significant changes were detected in the concentration of S-adenosylmethionine, the methyl-group donor in the synthesis of methylated phospholipids. The hypothesis that phospholipid methylation is obligatory for receptor-mediated Ca signals is not supported by these data and requires critical re-evaluation.

Full text

PDF
675

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akesson B. Structural requirements of the phospholipid substrate for phospholipid N-methylation in rat liver. Biochim Biophys Acta. 1983 Aug 1;752(3):460–466. [PubMed] [Google Scholar]
  2. Baldessarini R. J., Kopin I. J. S-adenosylmethionine in brain and other tissues. J Neurochem. 1966 Aug;13(8):769–777. doi: 10.1111/j.1471-4159.1966.tb09884.x. [DOI] [PubMed] [Google Scholar]
  3. Bareis D. L., Hirata F., Schiffmann E., Axelrod J. Phospholipid metabolism, calcium flux, and the receptor-mediated induction of chemotaxis in rabbit neutrophils. J Cell Biol. 1982 Jun;93(3):690–697. doi: 10.1083/jcb.93.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bareis D. L., Manganiello V. C., Hirata F., Vaughan M., Axelrod J. Bradykinin stimulates phospholipid methylation, calcium influx, prostaglandin formation, and cAMP accumulation in human fibroblasts. Proc Natl Acad Sci U S A. 1983 May;80(9):2514–2518. doi: 10.1073/pnas.80.9.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barsumian E. L., Isersky C., Petrino M. G., Siraganian R. P. IgE-induced histamine release from rat basophilic leukemia cell lines: isolation of releasing and nonreleasing clones. Eur J Immunol. 1981 Apr;11(4):317–323. doi: 10.1002/eji.1830110410. [DOI] [PubMed] [Google Scholar]
  6. Beaven M. A., Aiken D. L., Woldemussie E., Soll A. H. Changes in histamine synthetic activity, histamine content and responsiveness to compound 48/80 with maturation of rat peritoneal mast cells. J Pharmacol Exp Ther. 1983 Mar;224(3):620–626. [PubMed] [Google Scholar]
  7. Berridge M. J. 5-Hydroxytryptamine stimulation of phosphatidylinositol hydrolysis and calcium signalling in the blowfly salivary gland. Cell Calcium. 1982 Oct;3(4-5):385–397. doi: 10.1016/0143-4160(82)90025-2. [DOI] [PubMed] [Google Scholar]
  8. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Berridge M. J., Downes C. P., Hanley M. R. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982 Sep 15;206(3):587–595. doi: 10.1042/bj2060587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Betel I., van den Berg K. J. Interaction of concanavalin A with rat lymphocytes. Eur J Biochem. 1972 Nov 7;30(3):571–578. doi: 10.1111/j.1432-1033.1972.tb02128.x. [DOI] [PubMed] [Google Scholar]
  11. Bougnoux P., Bonvini E., Stevenson H. C., Markey S., Zatz M., Hoffman T. Identification of ubiquinone-50 as the major methylated nonpolar lipid in human monocytes. Regulation of its biosynthesis via methionine-dependent pathways and relationship to superoxide production. J Biol Chem. 1983 Apr 10;258(7):4339–4344. [PubMed] [Google Scholar]
  12. Cockcroft S., Gomperts B. D. Evidence for a role of phosphatidylinositol turnover in stimulus-secretion coupling. Studies with rat peritoneal mast cells. Biochem J. 1979 Mar 15;178(3):681–687. doi: 10.1042/bj1780681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cockcroft S. Phosphatidylinositol metabolism in mast cells and neutrophils. Cell Calcium. 1982 Oct;3(4-5):337–349. doi: 10.1016/0143-4160(82)90021-5. [DOI] [PubMed] [Google Scholar]
  14. Conrad D. H., Bazin H., Sehon A. H., Froese A. Binding parameters of the interaction between rat IgE and rat mast cell receptors. J Immunol. 1975 Jun;114(6):1688–1691. [PubMed] [Google Scholar]
  15. Coutts S. M., Nehring R. E., Jr, Jariwala N. U. Purification of rat peritoneal mast cells: occupation of IgE-receptors by IgE prevents loss of the receptors. J Immunol. 1980 May;124(5):2309–2315. [PubMed] [Google Scholar]
  16. Crews F. T., Morita Y., Hirata F., Axelrod J., Siraganian R. P. Phospholipid methylation affects immunoglobulin E-mediated histamine and arachidonic acid release in rat leukemia basophils. Biochem Biophys Res Commun. 1980 Mar 13;93(1):42–49. doi: 10.1016/s0006-291x(80)80243-9. [DOI] [PubMed] [Google Scholar]
  17. Crews F. T., Morita Y., McGivney A., Hirata F., Siraganian R. P., Axelrod J. IgE-mediated histamine release in rat basophilic leukemia cells: receptor activation, phospholipid methylation, Ca2+ flux, and release of arachidonic acid. Arch Biochem Biophys. 1981 Dec;212(2):561–571. doi: 10.1016/0003-9861(81)90399-4. [DOI] [PubMed] [Google Scholar]
  18. Cubero Robles E., van den Berg D. Synthesis of lecithins by acylation of O-(sn-glycero-3-phosphoryl) choline with fatty acid anhydrides. Biochim Biophys Acta. 1969 Dec 17;187(4):520–526. doi: 10.1016/0005-2760(69)90049-6. [DOI] [PubMed] [Google Scholar]
  19. German D. C., Bloch C. A., Kredich N. M. Measurements of S-adenosylmethionine and L-homocysteine metabolism in cultured human lymphoid cells. J Biol Chem. 1983 Sep 25;258(18):10997–11003. [PubMed] [Google Scholar]
  20. Hesketh T. R., Bavetta S., Smith G. A., Metcalfe J. C. Duration of the calcium signal in the mitogenic stimulation of thymocytes. Biochem J. 1983 Aug 15;214(2):575–579. doi: 10.1042/bj2140575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hesketh T. R., Smith G. A., Moore J. P., Taylor M. V., Metcalfe J. C. Free cytoplasmic calcium concentration and the mitogenic stimulation of lymphocytes. J Biol Chem. 1983 Apr 25;258(8):4876–4882. [PubMed] [Google Scholar]
  22. Hirata F., Axelrod J., Crews F. T. Concanavalin A stimulates phospholipid methylation and phosphatidylserine decarboxylation in rat mast cells. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4813–4816. doi: 10.1073/pnas.76.10.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hirata F., Axelrod J. Phospholipid methylation and biological signal transmission. Science. 1980 Sep 5;209(4461):1082–1090. doi: 10.1126/science.6157192. [DOI] [PubMed] [Google Scholar]
  24. Hirata F., Corcoran B. A., Venkatasubramanian K., Schiffmann E., Axelrod J. Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leukocytes. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2640–2643. doi: 10.1073/pnas.76.6.2640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hirata F., Toyoshima S., Axelrod J., Waxdal M. J. Phospholipid methylation: a biochemical signal modulating lymphocyte mitogenesis. Proc Natl Acad Sci U S A. 1980 Feb;77(2):862–865. doi: 10.1073/pnas.77.2.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hoffman D. R., Cornatzer W. E. Microsomal phosphatidylethanolamine methyltransferase: some physical and kinetic properties. Lipids. 1981 Jul;16(7):533–540. doi: 10.1007/BF02535052. [DOI] [PubMed] [Google Scholar]
  27. Hoffman T., Hirata F., Bougnoux P., Fraser B. A., Goldfarb R. H., Herberman R. B., Axelrod J. Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3839–3843. doi: 10.1073/pnas.78.6.3839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ishizaka T., Hirata F., Ishizaka K., Axelrod J. Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1903–1906. doi: 10.1073/pnas.77.4.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ishizaka T., Ishizaka K., Conrad D. H., Froese A. A new concept of triggering mechanisms of IgE-mediated histamine release. J Allergy Clin Immunol. 1978 May;61(5):320–330. doi: 10.1016/0091-6749(78)90054-4. [DOI] [PubMed] [Google Scholar]
  30. Ishizuka Y., Imai A., Nakashima S., Nozawa Y. Evidence for de novo synthesis of phosphatidylinositol coupled with histamine release in activated rat mast cells. Biochem Biophys Res Commun. 1983 Mar 16;111(2):581–587. doi: 10.1016/0006-291x(83)90346-7. [DOI] [PubMed] [Google Scholar]
  31. Keller R. Concanavalin A, a model "antigen" for the in vitro detection of cell-bound reaginic antibody in the rat. Clin Exp Immunol. 1973 Jan;13(1):139–147. [PMC free article] [PubMed] [Google Scholar]
  32. Kennerly D. A., Sullivan T. J., Parker C. W. Activation of phospholipid metabolism during mediator release from stimulated rat mast cells. J Immunol. 1979 Jan;122(1):152–159. [PubMed] [Google Scholar]
  33. Lombardini J. B., Talalay P. Formation, functions and regulatory importance of S-adenosyl-L-methionine. Adv Enzyme Regul. 1970;9:349–384. doi: 10.1016/s0065-2571(71)80054-7. [DOI] [PubMed] [Google Scholar]
  34. Maino V. C., Hayman M. J., Crumpton M. J. Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens. Biochem J. 1975 Jan;146(1):247–252. doi: 10.1042/bj1460247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Martin T. W., Lagunoff D. Interactions of lysophospholipids and mast cells. Nature. 1979 May 17;279(5710):250–252. doi: 10.1038/279250a0. [DOI] [PubMed] [Google Scholar]
  36. Mato J. M., Alemany S. What is the function of phospholipid N-methylation? Biochem J. 1983 Jul 1;213(1):1–10. doi: 10.1042/bj2130001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McClain D. A., Edelman G. M. Analysis of the stimulation-inhibition paradox exhibited by lymphocytes exposed to concanavalin A. J Exp Med. 1976 Dec 1;144(6):1494–1508. doi: 10.1084/jem.144.6.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. McGivney A., Crews F. T., Hirata F., Axelrod J., Siraganian R. P. Rat basophilic leukemia cell lines defective in phospholipid methyltransferase enzymes, Ca2+ influx, and histamine release: reconstitution by hybridization. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6176–6180. doi: 10.1073/pnas.78.10.6176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. McGivney A., Morita Y., Crews F. T., Hirata F., Axelrod J., Siraganian R. P. Phospholipase activation in the IgE-mediated and Ca2+ ionophore A23187-induced release of histamine from rat basophilic leukemia cells. Arch Biochem Biophys. 1981 Dec;212(2):572–580. doi: 10.1016/0003-9861(81)90400-8. [DOI] [PubMed] [Google Scholar]
  40. Michell R. H. Inositol lipid metabolism in dividing and differentiating cells. Cell Calcium. 1982 Oct;3(4-5):429–440. doi: 10.1016/0143-4160(82)90028-8. [DOI] [PubMed] [Google Scholar]
  41. Michell R. H. Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta. 1975 Mar 25;415(1):81–47. doi: 10.1016/0304-4157(75)90017-9. [DOI] [PubMed] [Google Scholar]
  42. Michell R. H. Is phosphatidylinositol really out of the calcium gate? Nature. 1982 Apr 8;296(5857):492–493. doi: 10.1038/296492a0. [DOI] [PubMed] [Google Scholar]
  43. Michell R. H., Kirk C. J., Jones L. M., Downes C. P., Creba J. A. The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions. Philos Trans R Soc Lond B Biol Sci. 1981 Dec 18;296(1080):123–138. doi: 10.1098/rstb.1981.0177. [DOI] [PubMed] [Google Scholar]
  44. Moore J. P., Smith G. A., Hesketh T. R., Metcalfe J. C. Early increases in phospholipid methylation are not necessary for the mitogenic stimulation of lymphocytes. J Biol Chem. 1982 Jul 25;257(14):8183–8189. [PubMed] [Google Scholar]
  45. Moore J. P., Smith G. A., Hesketh T. R., Metcalfe J. C. Large effects of preparative techniques on lymphocyte cyclic AMP content. Biochem J. 1983 Oct 15;216(1):207–213. doi: 10.1042/bj2160207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Morris J. D., Metcalfe J. C., Smith G. A., Hesketh T. R., Taylor M. V. Some mitogens cause rapid increases in free calcium in fibroblasts. FEBS Lett. 1984 Apr 24;169(2):189–193. doi: 10.1016/0014-5793(84)80316-6. [DOI] [PubMed] [Google Scholar]
  47. Parker C. W., Kelly J. P., Falkenhein S. F., Huber M. G. Release of arachidonic acid from human lymphocytes in response to mitogenic lectins. J Exp Med. 1979 Jun 1;149(6):1487–1503. doi: 10.1084/jem.149.6.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pearce F. L. Calcium and histamine secretion from mast cells. Prog Med Chem. 1982;19:59–109. doi: 10.1016/s0079-6468(08)70328-x. [DOI] [PubMed] [Google Scholar]
  49. Pozzan T., Corps A. N., Hesketh T. R., Metcalfe J. C. Mitogenic stimulation and the redistribution of concanavalin A receptors on lymphocytes. Exp Cell Res. 1981 Aug;134(2):399–408. doi: 10.1016/0014-4827(81)90439-0. [DOI] [PubMed] [Google Scholar]
  50. Resch K., Loracher A., Mähler B., Stoeck M., Rode H. N. Functional mosaicism of the lymphocyte plasma membrane. Characterization of membrane subfractions obtained by affinity chromatography on concanavalin A-sepharose. Biochim Biophys Acta. 1978 Aug 4;511(2):176–193. doi: 10.1016/0005-2736(78)90312-7. [DOI] [PubMed] [Google Scholar]
  51. Schellenberg R. R. Enhanced phospholipid metabolism in rat mast cells stimulated to release histamine. Immunology. 1980 Sep;41(1):123–129. [PMC free article] [PubMed] [Google Scholar]
  52. Smith G. A., Hesketh R. T., Metcalfe J. C., Feeney J., Morris P. G. Intracellular calcium measurements by 19F NMR of fluorine-labeled chelators. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7178–7182. doi: 10.1073/pnas.80.23.7178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Smith G. A., Hesketh T. R., Plumb R. W., Metcalfe J. C. The exogenous lipid requirement for histamine release from rat peritoneal mast cells stimulated by concanavalin A. FEBS Lett. 1979 Sep 1;105(1):58–62. doi: 10.1016/0014-5793(79)80887-x. [DOI] [PubMed] [Google Scholar]
  54. Sullivan T. J., Greene W. C., Parker C. W. Concanavalin A-induced histamine release from normal rat mast cells. J Immunol. 1975 Jul;115(1):278–282. [PubMed] [Google Scholar]
  55. Tsien R. Y. A non-disruptive technique for loading calcium buffers and indicators into cells. Nature. 1981 Apr 9;290(5806):527–528. doi: 10.1038/290527a0. [DOI] [PubMed] [Google Scholar]
  56. Tsien R. Y. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry. 1980 May 27;19(11):2396–2404. doi: 10.1021/bi00552a018. [DOI] [PubMed] [Google Scholar]
  57. Tsien R. Y., Pozzan T., Rink T. J. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature. 1982 Jan 7;295(5844):68–71. doi: 10.1038/295068a0. [DOI] [PubMed] [Google Scholar]
  58. Vance D. E., de Kruijff B. The possible functional significance of phosphatidylethanolamine methylation. Nature. 1980 Nov 20;288(5788):277–279. doi: 10.1038/288277a0. [DOI] [PubMed] [Google Scholar]
  59. Zatz M., Dudley P. A., Kloog Y., Markey S. P. Nonpolar lipid methylation. Biosynthesis of fatty acid methyl esters by rat lung membranes using S-adenosylmethionine. J Biol Chem. 1981 Oct 10;256(19):10028–10032. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES