Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Biochemical Journal logoLink to Biochemical Journal
. 1988 Aug 1;253(3):827–833. doi: 10.1042/bj2530827

AlF4- reversibly inhibits 'P'-type cation-transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase.

L Missiaen 1, F Wuytack 1, H De Smedt 1, M Vrolix 1, R Casteels 1
PMCID: PMC1149377  PMID: 2845938

Abstract

The only known cellular action of AlF4- is to stimulate the G-proteins. The aim of the present work is to demonstrate that AlF4- also inhibits 'P'-type cation-transport ATPases. NaF plus AlCl3 completely and reversibly inhibits the activity of the purified (Na+ + K+)-ATPase (Na+- and K+-activated ATPase) and of the purified plasmalemmal (Ca2+ + Mg2+)-ATPase (Ca2+-stimulated and Mg2+-dependent ATPase). It partially inhibits the activity of the sarcoplasmic-reticulum (Ca2+ + Mg2+)-ATPase, whereas it does not affect the mitochondrial H+-transporting ATPase. The inhibitory substances are neither F- nor Al3+ but rather fluoroaluminate complexes. Because AlF4- still inhibits the ATPase in the presence of guanosine 5'-[beta-thio]diphosphate, and because guanosine 5'-[beta gamma-imido]triphosphate does not inhibit the ATPase, it is unlikely that the inhibition could be due to the activation of an unknown G-protein. The time course of inhibition and the concentrations of NaF and AlCl3 required for this inhibition differ for the different ATPases. AlF4- inhibits the (Na+ + K+)-ATPase and the plasmalemmal (Ca2+ + Mg2+)-ATPase noncompetitively with respect to ATP and to their respective cationic substrates, Na+ and Ca2+. AlF4- probably binds to the phosphate-binding site of the ATPase, as the Ki for inhibition of the (Na+ + K+)-ATPase and of the plasmalemmal (Ca2+ + Mg2+)-ATPase is shifted in the presence of respectively 5 and 50 mM-Pi to higher concentrations of NaF. Moreover, AlF4- inhibits the K+-activated p-nitrophenylphosphatase of the (Na+ + K+)-ATPase competitively with respect to p-nitrophenyl phosphate. This AlF4- -induced inhibition of 'P'-type cation-transport ATPases warns us against explaining all the effects of AlF4- on intact cells by an activation of G-proteins.

Full text

PDF
827

Selected References

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

  1. Bigay J., Deterre P., Pfister C., Chabre M. Fluoride complexes of aluminium or beryllium act on G-proteins as reversibly bound analogues of the gamma phosphate of GTP. EMBO J. 1987 Oct;6(10):2907–2913. doi: 10.1002/j.1460-2075.1987.tb02594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blackmore P. F., Bocckino S. B., Waynick L. E., Exton J. H. Role of a guanine nucleotide-binding regulatory protein in the hydrolysis of hepatocyte phosphatidylinositol 4,5-bisphosphate by calcium-mobilizing hormones and the control of cell calcium. Studies utilizing aluminum fluoride. J Biol Chem. 1985 Nov 25;260(27):14477–14483. [PubMed] [Google Scholar]
  3. 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]
  4. Bokoch G. M., Katada T., Northup J. K., Hewlett E. L., Gilman A. G. Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem. 1983 Feb 25;258(4):2072–2075. [PubMed] [Google Scholar]
  5. Brandt D. R., Ross E. M. Effect of Al3+ plus F- on the catecholamine-stimulated GTPase activity of purified and reconstituted Gs. Biochemistry. 1986 Nov 4;25(22):7036–7041. doi: 10.1021/bi00370a042. [DOI] [PubMed] [Google Scholar]
  6. Gopalakrishna R., Anderson W. B. Ca2+-induced hydrophobic site on calmodulin: application for purification of calmodulin by phenyl-Sepharose affinity chromatography. Biochem Biophys Res Commun. 1982 Jan 29;104(2):830–836. doi: 10.1016/0006-291x(82)90712-4. [DOI] [PubMed] [Google Scholar]
  7. Guillon G., Mouillac B., Balestre M. N. Activation of polyphosphoinositide phospholipase C by fluoride in WRK1 cell membranes. FEBS Lett. 1986 Aug 18;204(2):183–188. doi: 10.1016/0014-5793(86)80808-0. [DOI] [PubMed] [Google Scholar]
  8. Hepler J. R., Harden T. K. Guanine nucleotide-dependent pertussis-toxin-insensitive stimulation of inositol phosphate formation by carbachol in a membrane preparation from human astrocytoma cells. Biochem J. 1986 Oct 1;239(1):141–146. doi: 10.1042/bj2390141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hughes B. P., Barritt G. J. The stimulation by sodium fluoride of plasma-membrane Ca2+ inflow in isolated hepatocytes. Evidence that a GTP-binding regulatory protein is involved in the hormonal stimulation of Ca2+ inflow. Biochem J. 1987 Jul 1;245(1):41–47. doi: 10.1042/bj2450041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jones L. R., Cala S. E. Biochemical evidence for functional heterogeneity of cardiac sarcoplasmic reticulum vesicles. J Biol Chem. 1981 Nov 25;256(22):11809–11818. [PubMed] [Google Scholar]
  11. Kanaho Y., Moss J., Vaughan M. Mechanism of inhibition of transducin GTPase activity by fluoride and aluminum. J Biol Chem. 1985 Sep 25;260(21):11493–11497. [PubMed] [Google Scholar]
  12. Katada T., Bokoch G. M., Northup J. K., Ui M., Gilman A. G. The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Properties and function of the purified protein. J Biol Chem. 1984 Mar 25;259(6):3568–3577. [PubMed] [Google Scholar]
  13. Katada T., Northup J. K., Bokoch G. M., Ui M., Gilman A. G. The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and guanine nucleotide-dependent hormonal inhibition. J Biol Chem. 1984 Mar 25;259(6):3578–3585. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Litosch I. Guanine nucleotide and NaF stimulation of phospholipase C activity in rat cerebral-cortical membranes. Studies on substrate specificity. Biochem J. 1987 May 15;244(1):35–40. doi: 10.1042/bj2440035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Northup J. K., Smigel M. D., Sternweis P. C., Gilman A. G. The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution of the activated 45,000-dalton (alpha) subunit. J Biol Chem. 1983 Sep 25;258(18):11369–11376. [PubMed] [Google Scholar]
  17. Ray T. K., Forte J. G. Studies on the phosphorylated intermediates of a K+-stimulated ATPase from rabbit gastric mucosa. Biochim Biophys Acta. 1976 Sep 7;443(3):451–467. doi: 10.1016/0005-2736(76)90465-x. [DOI] [PubMed] [Google Scholar]
  18. Robinson J. D., Davis R. L., Steinberg M. Fluoride and beryllium interact with the (Na + K)-dependent ATPase as analogs of phosphate. J Bioenerg Biomembr. 1986 Dec;18(6):521–531. doi: 10.1007/BF00743148. [DOI] [PubMed] [Google Scholar]
  19. Schuurmans Stekhoven F., Bonting S. L. Transport adenosine triphosphatases: properties and functions. Physiol Rev. 1981 Jan;61(1):1–76. doi: 10.1152/physrev.1981.61.1.1. [DOI] [PubMed] [Google Scholar]
  20. Seifert R., Rosenthal W., Schultz G. Guanine nucleotides stimulate NADPH oxidase in membranes of human neutrophils. FEBS Lett. 1986 Sep 1;205(1):161–165. doi: 10.1016/0014-5793(86)80886-9. [DOI] [PubMed] [Google Scholar]
  21. Sternweis P. C., Gilman A. G. Aluminum: a requirement for activation of the regulatory component of adenylate cyclase by fluoride. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4888–4891. doi: 10.1073/pnas.79.16.4888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Strnad C. F., Parente J. E., Wong K. Use of fluoride ion as a probe for the guanine nucleotide-binding protein involved in the phosphoinositide-dependent neutrophil transduction pathway. FEBS Lett. 1986 Sep 29;206(1):20–24. doi: 10.1016/0014-5793(86)81332-1. [DOI] [PubMed] [Google Scholar]
  23. Taylor C. W., Merritt J. E., Putney J. W., Jr, Rubin R. P. A guanine nucleotide-dependent regulatory protein couples substance P receptors to phospholipase C in rat parotid gland. Biochem Biophys Res Commun. 1986 Apr 14;136(1):362–368. doi: 10.1016/0006-291x(86)90919-8. [DOI] [PubMed] [Google Scholar]
  24. Verbist J., Wuytack F., De Schutter G., Raeymaekers L., Casteels R. Reconstitution of the purified calmodulin-dependent (Ca2+ + Mg2+)-ATPase from smooth muscle. Cell Calcium. 1984 Jun;5(3):253–263. doi: 10.1016/0143-4160(84)90040-x. [DOI] [PubMed] [Google Scholar]
  25. Verma A. K., Penniston J. T. Two Ca2+-requiring p-nitrophenylphosphatase activities of the highly purified Ca2+-pumping adenosinetriphosphatase of human erythrocyte membranes, one requiring calmodulin and the other ATP. Biochemistry. 1984 Oct 9;23(21):5010–5015. doi: 10.1021/bi00316a028. [DOI] [PubMed] [Google Scholar]
  26. Wuytack F., Casteels R. Demonstration of a (Ca2+ + Mg2+)-ATPase activity probably related to Ca2+ transport in the microsomal fraction of porcine coronary artery smooth muscle. Biochim Biophys Acta. 1980 Jan 25;595(2):257–263. doi: 10.1016/0005-2736(80)90088-7. [DOI] [PubMed] [Google Scholar]
  27. de Smedt H., Borghgraef R., Ceuterick F., Heremans K. Pressure effects on lipid-protein interactions in (NA+ + K+)-ATPase. Biochim Biophys Acta. 1979 Oct 5;556(3):479–489. doi: 10.1016/0005-2736(79)90135-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES