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. 1992 Apr 1;283(Pt 1):21–24. doi: 10.1042/bj2830021

Phosphorylation by casein kinase II alters the biological activity of calmodulin.

D B Sacks 1, H W Davis 1, J P Williams 1, E L Sheehan 1, J G Garcia 1, J M McDonald 1
PMCID: PMC1130984  PMID: 1314563

Abstract

Calmodulin is the major intracellular Ca(2+)-binding protein, providing Ca(2+)-dependent regulation of numerous intracellular enzymes. The phosphorylation of calmodulin may provide an additional mechanism for modulating its function as a signal transducer. Phosphocalmodulin has been identified in tissues and cells, and calmodulin is phosphorylated both in vitro and in intact cells by various enzymes. Phosphorylation of calmodulin on serine/threonine residues by casein kinase II decreases its ability to activate both myosin-light-chain kinase and cyclic nucleotide phosphodiesterase. For myosin-light-chain kinase the primary effect is an inhibition of the Vmax. of the reaction, with no apparent change in the concentration at which half-maximal velocity is attained (K0.5) for either Ca2+ or calmodulin. In contrast, for phosphodiesterase, phosphorylation of calmodulin significantly increases the K0.5 for calmodulin without noticeably altering the Vmax. or the K0.5 for Ca2+. The higher the stoichiometry of phosphorylation of calmodulin, the greater the inhibition of calmodulin-stimulated activity for both enzymes. Therefore the phosphorylation of calmodulin by casein kinase II appears to provide a Ca(2+)-independent mechanism whereby calmodulin regulates at least two important target enzymes, myosin-light-chain kinase and cyclic nucleotide phosphodiesterase.

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Selected References

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

  1. Ackerman P., Glover C. V., Osheroff N. Stimulation of casein kinase II by epidermal growth factor: relationship between the physiological activity of the kinase and the phosphorylation state of its beta subunit. Proc Natl Acad Sci U S A. 1990 Jan;87(2):821–825. doi: 10.1073/pnas.87.2.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Cheung W. Y. Calmodulin plays a pivotal role in cellular regulation. Science. 1980 Jan 4;207(4426):19–27. doi: 10.1126/science.6243188. [DOI] [PubMed] [Google Scholar]
  4. Colca J. R., DeWald D. B., Pearson J. D., Palazuk B. J., Laurino J. P., McDonald J. M. Insulin stimulates the phosphorylation of calmodulin in intact adipocytes. J Biol Chem. 1987 Aug 25;262(24):11399–11402. [PubMed] [Google Scholar]
  5. Craig T. A., Watterson D. M., Prendergast F. G., Haiech J., Roberts D. M. Site-specific mutagenesis of the alpha-helices of calmodulin. Effects of altering a charge cluster in the helix that links the two halves of calmodulin. J Biol Chem. 1987 Mar 5;262(7):3278–3284. [PubMed] [Google Scholar]
  6. Fukami Y., Nakamura T., Nakayama A., Kanehisa T. Phosphorylation of tyrosine residues of calmodulin in Rous sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4190–4193. doi: 10.1073/pnas.83.12.4190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gagnon C., Kelly S., Manganiello V., Vaughan M., Odya C., Strittmatter W., Hoffman A., Hirata F. Modification of calmodulin function by enzymatic carboxylic methylation. Nature. 1981 Jun 11;291(5815):515–516. doi: 10.1038/291515a0. [DOI] [PubMed] [Google Scholar]
  8. Garone L., Albaugh S., Steiner R. F. The secondary structure of turkey gizzard myosin light chain kinase and the nature of its interaction with calmodulin. Biopolymers. 1990;30(11-12):1139–1149. doi: 10.1002/bip.360301113. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Graves C. B., Gale R. D., Laurino J. P., McDonald J. M. The insulin receptor and calmodulin. Calmodulin enhances insulin-mediated receptor kinase activity and insulin stimulates phosphorylation of calmodulin. J Biol Chem. 1986 Aug 5;261(22):10429–10438. [PubMed] [Google Scholar]
  11. Hathaway D. R., Adelstein R. S. Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1653–1657. doi: 10.1073/pnas.76.4.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hathaway G. M., Traugh J. A. Casein kinase II. Methods Enzymol. 1983;99:317–331. doi: 10.1016/0076-6879(83)99067-5. [DOI] [PubMed] [Google Scholar]
  13. Haystead T. A., Campbell D. G., Hardie D. G. Analysis of sites phosphorylated on acetyl-CoA carboxylase in response to insulin in isolated adipocytes. Comparison with sites phosphorylated by casein kinase-2 and the calmodulin-dependent multiprotein kinase. Eur J Biochem. 1988 Aug 1;175(2):347–354. doi: 10.1111/j.1432-1033.1988.tb14203.x. [DOI] [PubMed] [Google Scholar]
  14. Heppel L. A., Newton D. L., Klee C. B., Draetta G. F. The phosphorylation of calmodulin and calmodulin fragments by kinase fractions from bovine brain. Biochim Biophys Acta. 1988 Oct 28;972(1):69–78. doi: 10.1016/0167-4889(88)90104-8. [DOI] [PubMed] [Google Scholar]
  15. Johnson J. D., Walters J. D., Mills J. S. A continuous fluorescence assay for cyclic nucleotide phosphodiesterase hydrolysis of cyclic GMP. Anal Biochem. 1987 Apr;162(1):291–295. doi: 10.1016/0003-2697(87)90039-x. [DOI] [PubMed] [Google Scholar]
  16. Klarlund J. K., Czech M. P. Insulin-like growth factor I and insulin rapidly increase casein kinase II activity in BALB/c 3T3 fibroblasts. J Biol Chem. 1988 Nov 5;263(31):15872–15875. [PubMed] [Google Scholar]
  17. Klee C. B., Crouch T. H., Richman P. G. Calmodulin. Annu Rev Biochem. 1980;49:489–515. doi: 10.1146/annurev.bi.49.070180.002421. [DOI] [PubMed] [Google Scholar]
  18. Kotagal N., Colca J. R., McDaniel M. L. Activation of an islet cell plasma membrane (Ca2+ + Mg2+)-ATPase by calmodulin and Ca-EGTA. J Biol Chem. 1983 Apr 25;258(8):4808–4813. [PubMed] [Google Scholar]
  19. Kubo M., Strott C. A. Phosphorylation of calmodulin on threonine residue(s) by cytosol prepared from the adrenal cortex. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1333–1339. doi: 10.1016/s0006-291x(88)80778-2. [DOI] [PubMed] [Google Scholar]
  20. Manalan A. S., Klee C. B. Affinity selection of chemically modified proteins: role of lysyl residues in the binding of calmodulin to calcineurin. Biochemistry. 1987 Mar 10;26(5):1382–1390. doi: 10.1021/bi00379a026. [DOI] [PubMed] [Google Scholar]
  21. Meggio F., Brunati A. M., Pinna L. A. Polycation-dependent, Ca2+-antagonized phosphorylation of calmodulin by casein kinase-2 and a spleen tyrosine protein kinase. FEBS Lett. 1987 May 11;215(2):241–246. doi: 10.1016/0014-5793(87)80154-0. [DOI] [PubMed] [Google Scholar]
  22. Nakajo S., Hayashi K., Daimatsu T., Tanaka M., Nakaya K., Nakamura Y. Phosphorylation of rat brain calmodulin in vivo and in vitro. Biochem Int. 1986 Oct;13(4):687–693. [PubMed] [Google Scholar]
  23. Persechini A., Blumenthal D. K., Jarrett H. W., Klee C. B., Hardy D. O., Kretsinger R. H. The effects of deletions in the central helix of calmodulin on enzyme activation and peptide binding. J Biol Chem. 1989 May 15;264(14):8052–8058. [PubMed] [Google Scholar]
  24. Plancke Y. D., Lazarides E. Evidence for a phosphorylated form of calmodulin in chicken brain and muscle. Mol Cell Biol. 1983 Aug;3(8):1412–1420. doi: 10.1128/mcb.3.8.1412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sacks D. B., Fujita-Yamaguchi Y., Gale R. D., McDonald J. M. Tyrosine-specific phosphorylation of calmodulin by the insulin receptor kinase purified from human placenta. Biochem J. 1989 Nov 1;263(3):803–812. doi: 10.1042/bj2630803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sacks D. B., McDonald J. M. Calmodulin as substrate for insulin-receptor kinase. Phosphorylation by receptors from rat skeletal muscle. Diabetes. 1989 Jan;38(1):84–90. doi: 10.2337/diab.38.1.84. [DOI] [PubMed] [Google Scholar]
  27. Sacks D. B., McDonald J. M. Insulin-stimulated phosphorylation of calmodulin by rat liver insulin receptor preparations. J Biol Chem. 1988 Feb 15;263(5):2377–2383. [PubMed] [Google Scholar]
  28. Sommercorn J., Mulligan J. A., Lozeman F. J., Krebs E. G. Activation of casein kinase II in response to insulin and to epidermal growth factor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8834–8838. doi: 10.1073/pnas.84.24.8834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tuazon P. T., Traugh J. A. Casein kinase I and II--multipotential serine protein kinases: structure, function, and regulation. Adv Second Messenger Phosphoprotein Res. 1991;23:123–164. [PubMed] [Google Scholar]
  30. Weber P. C., Lukas T. J., Craig T. A., Wilson E., King M. M., Kwiatkowski A. P., Watterson D. M. Computational and site-specific mutagenesis analyses of the asymmetric charge distribution on calmodulin. Proteins. 1989;6(1):70–85. doi: 10.1002/prot.340060107. [DOI] [PubMed] [Google Scholar]

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