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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1975 Jan;72(1):64–68. doi: 10.1073/pnas.72.1.64

Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase.

C O Brostrom, Y C Huang, B M Breckenridge, D J Wolff
PMCID: PMC432241  PMID: 164029

Abstract

An activating factor of adenylate cyclase (EC 4.6.1.1) HAS BEEN OBTAINED FROM DETERGENT-DISPERSED PREPARATIONS OF PORCINE CEREBRAL CORTEX BY COLUMN CHROMATOGRAPHY ON ECTEOLA-cellulose. The factor was identified by acrylamide gel electrophoresis and by enzyme activation studies as the Ca2+-binding protein that regulates the activity of a brain cyclic nucleotide phosphodiesterase. This Ca2+-binding protein confers a Ca2+-dependent activation upon the adenylate cyclase, which is reversed by the subsequent addition of egta in excess of the free Ca2+. It is proposed that this Ca2+-dependent regulator controls enzymatic activities responsible for the synthesis of adenosine 3':5'-monophosphate and for the hydrolysis of guanosine 3':5'-monophosphate.

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Selected References

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

  1. Baker P. F., Hodgkin A. L., Ridgway E. B. Depolarization and calcium entry in squid giant axons. J Physiol. 1971 Nov;218(3):709–755. doi: 10.1113/jphysiol.1971.sp009641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bitensky M. W., Gorman R. E. Cellular responses to cyclic AMP. Prog Biophys Mol Biol. 1973;26:409–461. doi: 10.1016/0079-6107(73)90023-0. [DOI] [PubMed] [Google Scholar]
  3. Bradham L. S. Comparison of the effects of Ca 2+ and Mg 2+ on the adenyl cyclase of beef brain. Biochim Biophys Acta. 1972 Aug 28;276(2):434–443. doi: 10.1016/0005-2744(72)91005-4. [DOI] [PubMed] [Google Scholar]
  4. Bär H. P., Hechter O. Adenyl cyclase and hormone action. 3. Calcium requirement for ACTH stimulation of adenyl cyclase. Biochem Biophys Res Commun. 1969 Jun 6;35(5):681–686. doi: 10.1016/0006-291x(69)90459-8. [DOI] [PubMed] [Google Scholar]
  5. Cheung W. Y. Cyclic 3',5'-nucleotide phosphodiesterase. Evidence for and properties of a protein activator. J Biol Chem. 1971 May 10;246(9):2859–2869. [PubMed] [Google Scholar]
  6. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  7. Johnson R. A., Sutherland E. W. Detergent-dispersed adenylate cyclase from rat brain. Effects of fluoride, cations, and chelators. J Biol Chem. 1973 Jul 25;248(14):5114–5121. [PubMed] [Google Scholar]
  8. Kakiuchi S., Yamazaki R., Teshima Y., Uenishi K. Regulation of nucleoside cyclic 3':5'-monophosphate phosphodiesterase activity from rat brain by a modulator and Ca2+. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3526–3530. doi: 10.1073/pnas.70.12.3526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kram R., Tomkins G. M. Pleiotypic control by cyclic AMP: interaction with cyclic GMP and possible role of microtubules. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1659–1663. doi: 10.1073/pnas.70.6.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
  11. 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]
  12. Lefkowitz R. J., Roth J., Pastan I. Effects of calcium on ACTH stimulation of the adrenal: separation of hormone binding from adenyl cyclase activation. Nature. 1970 Nov 28;228(5274):864–866. doi: 10.1038/228864a0. [DOI] [PubMed] [Google Scholar]
  13. Nakazawa K., Sano M. Studies on guanylate cyclase. A new assay method for guanylate cyclase and properties of the cyclase from rat brain. J Biol Chem. 1974 Jul 10;249(13):4207–4211. [PubMed] [Google Scholar]
  14. Seifert W. E., Rudland P. S. Possible involvement of cyclic GMP in growth control of cultured mouse cells. Nature. 1974 Mar 8;248(5444):138–140. doi: 10.1038/248138a0. [DOI] [PubMed] [Google Scholar]
  15. Shimizu H., Creveling C. R., Daly J. W. Cyclic adenosine 3',5'-monophosphate formation in brain slices: stimulation by batrachotoxin, ouabain, veratridine, and potassium ions. Mol Pharmacol. 1970 Mar;6(2):184–188. [PubMed] [Google Scholar]
  16. Teo T. S., Wang T. H., Wang J. H. Purification and properties of the protein activator of bovine heart cyclic adenosine 3',5'-monophosphate phosphodiesterase. J Biol Chem. 1973 Jan 25;248(2):588–595. [PubMed] [Google Scholar]
  17. Von Hungen K., Roberts S. Catecholamine and Ca 2+ activation of adenylate cyclase systems in synaptosomal fractions from rat cerebral cortex. Nat New Biol. 1973 Mar 14;242(115):58–60. doi: 10.1038/newbio242058a0. [DOI] [PubMed] [Google Scholar]
  18. Wolff D. J., Brostrom C. O. Calcium-binding phosphoprotein from pig brain: identification as a calcium-dependent regulator of brain cyclic nucleotide phosphodiesterase. Arch Biochem Biophys. 1974 Jul;163(1):349–358. doi: 10.1016/0003-9861(74)90486-x. [DOI] [PubMed] [Google Scholar]
  19. Wolff D. J., Huebner J. A., Siegel F. L. Calcium-binding phosphoprotein of pig brain: effects of cations on the calcium binding. J Neurochem. 1972 Dec;19(12):2855–2862. doi: 10.1111/j.1471-4159.1972.tb03823.x. [DOI] [PubMed] [Google Scholar]
  20. Wolff D. J., Siegel F. L. Purification of a calcium-binding phosphoprotein from pig brain. J Biol Chem. 1972 Jul 10;247(13):4180–4185. [PubMed] [Google Scholar]
  21. Zanella J., Jr, Rall T. W. Evaluation of electrical pulses and elevated levels of potassium ions as stimulants of adenosine 3', 5'-monophosphate (cyclic AMP) accumulation in guinea-pig brain. J Pharmacol Exp Ther. 1973 Aug;186(2):241–252. [PubMed] [Google Scholar]

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