Skip to main content
SpringerLink
Log in

The role of phospholamban in the regulation of calcium transport by cardiac sarcoplasmic reticulum

  • Invited Paper
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The calcium transport mechanism of cardiac sarcoplasmic reticulum (SR) is regulated by a phosphoregulatory mechanism involving the phosphorylation-dephosphorylation of an integral membrane component, termed phospholamban. Phospholamban, a 27,000 Da proteolipid, contains phosphorylation sites for three independent protein kinases: 1) cAMP-dependent, 2) Ca2+-calmodulin-dependent, and 3) Ca2+-phospholipid-dependent. Phosphorylation of phospholamban by any one of these kinases is associated with stimulation of the calcium transport rates in isolated SR vesicles. Dephosphorylation of phosphorylated phospholamban results in the reversal of the stimulatory effects produced by the protein kinases. Studies conducted on perfused hearts have shown that during exposure to beta-adrenergic agents, a good correlation exists between the in situ phosphorylation of phospholamban and the relaxation of the left ventricle. Phosphorylation of phospholamban in situ is also associated with stimulation of calcium transport rates by cardiac SR, similar to in vitro findings. Removal of beta-adrenergic agents results in the reversal of the inotropic response and this is associated with dephosphorylation of phospholamban. These findings indicate that a phospho-regulatory mechanism involving phospholamban may provide at least one of the controls for regulation of the contractile properties of the myocardium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wegener AD, Jones LR: Phosphorylation-induced mobility shift in phospholamban in sodium dodecyl sulfate-polyacrylamide gels. J Biol Chem 259: 1834–1841, 1984

    Google Scholar 

  2. Gasser JT, Chiesi MP, Carafoli E: Concerted phosphorylation of the 26-kilodalton phospholamban oligomer and of the low molecular weight phospholamban subunits. Biochemistry 25: 7615–7623, 1986

    Google Scholar 

  3. Fujii J, Ueno A, Kitano K, Tanaka S, Kadoma M, Tada M: Complete complementary DNA-derived amino acid sequence of canine cardiac phospholamban. J Clin Invest 79: 301–304, 1987

    Google Scholar 

  4. Jones LR, Simmerman HKB, Wilson WW, Gurd FRN, Wegener AD: Purification and characterization of phospholamban from canine cardiac sarcoplasmic reticulum. J Biol Chem 260: 7721–7730, 1985

    Google Scholar 

  5. Kirchberger MA, Tada M, Katz AM: Adenosine 3′:5′monophosphate-dependent protein kinase — catalyzed phosphorylation reaction and its relationship to calcium transport in cardiac sarcoplasmic reticulum. J Biol Chem 249: 6166–6173, 1974

    Google Scholar 

  6. Kranias EG: Regulation of Ca2+ transport by cyclic 3′,5′AMP-dependent and calcium-calmodulin-dependent phosphorylation of cardiac sarcoplasmic reticulum. Biochim Biophys Acta 844: 193–199, 1985

    Google Scholar 

  7. Kranias EG, Mandel F, Wang T, Schwartz A: Mechanism of the stimulation of calcium ion dependent adenosine triphosphatase of cardiac sarcoplasmic reticulum by adenosine 3′,5′-monophosphate-dependent protein kinase. Biochemistry 19: 5434–5439, 1980

    Google Scholar 

  8. Kranias EG, Schwartz A, Jungmann RA: Characterization of cyclic 3′:5′-AMP-dependent protein kinase in sarcoplasmic reticulum and cytosol of canine myocardium. Biochim Biophys Acta 709: 28–37, 1982

    Google Scholar 

  9. Kranias EG, Bilezikjian LM, Potter JD, Piascik MT, Schwartz A: The role of calmodulin in regulation of cardiac sarcoplasmic reticulum phosphorylation. Ann NY Acad Sci 365: 279–291, 1980

    Google Scholar 

  10. Davis BA, Schwartz A, Samaha FJ, Kranias EG: Regulation of cardiac sarcoplasmic reticulum calcium transport by calcium-calmodulin-dependent phosphorylation. J Biol Chem 258: 13587–13591, 1983

    Google Scholar 

  11. Gupta RC, Kranias EG: Purification and characterization of a calcium-calmodulin-dependent phospholamban kinase from canine myocardium. Biochemistry 28: 5909–5916, 1989

    Google Scholar 

  12. Kranias EG: Regulation of calcium transport by protein phosphatasc activity associated with cardiac sarcoplasmic reticulum. J Biol Chem 260: 11006–11010, 1985

    Google Scholar 

  13. Kranias EG, Di Salvo J: A phospholamban protein phosphatase activity associated with cardiac sarcoplasmic reticulum. J Biol Chem 261: 10029–10032, 1986

    Google Scholar 

  14. Kranias EG, Steenaart NAE, Di Salvo J: Purification and characterization of phospholamban phosphatase from cardiac muscle. J Biol Chem 263: 15681–15687, 1988

    Google Scholar 

  15. Jakab G, Kranias EG: Phosphorylation and dephosphorylation of purified phospholamban and associated phosphatidylinositides. Biochemistry 27: 3799–3806, 1988

    Google Scholar 

  16. Young EF, McKee MJ, Ferguson DG, Kranias EG: Structural characterization of phospholamban in cardiac sarcoplasmic reticulum membranes by crosslinking. Memb Biochemistry, in press, 1990

  17. Lamers JMJ, Stinis JT: Phosphorylation of low molecular weight proteins in purified preparations of rat heart sarcolemma and sarcoplasmic reticulum. Biochim Biophys Acta 624: 443–459, 1980

    Google Scholar 

  18. Simmerman HKB, Collins JH, Theibert JL, Wegener AD, Jones LR: Sequence analysis of phospholamban. Identification of phosphorylation sites and two major structural domains. J Biol Chem 261: 13333–13341, 1986

    Google Scholar 

  19. Kovacs RJ, Nelson MT, Simmerman HKB, Jones LK: Phospholamban forms Ca2+-selective channels in lipid bilayers. J Biol Chem 263: 18364–18368, 1988

    Google Scholar 

  20. Kranias EG, Garvey JL, Srivastava RD, Solaro RJ: Phosphorylation and functional modifications of sarcoplasmic reticulum and myofibrils in isolated rabbit hearts stimulated with isoprenaline. Biochem J 226: 113–121, 1985

    Google Scholar 

  21. Potter JD, Holroyde HJ, Robertson SP, Solaro RJ, Kranias EG, Johnson JD: The regulation of cardiac-muscle contraction by Troponin. In: Dowben RM, Shay JW (eds) Cell and Muscle Motility, vol 2, pmPlenum Publishing Co, 1982, pp 245–255

  22. Kranias EG, Solaro RJ: Coordination of cardiac sarcoplasmic reticulum and myofibrillar function by protein phosphorylation. Fed Proc 42: 33–38, 1983

    Google Scholar 

  23. Grand RIA, Perry SV: Calmodulin-binding proteins from brain and other tissues. Biochem J 183: 285–295, 1979

    Google Scholar 

  24. Lindemann JP, Watanabe AM: Phosphorylation of phospholamban in intact myocardium. Role of Ca2+-calmodulin-dependent mechanisms. J Biol Chem 260: 4516–4525, 1985

    Google Scholar 

Download references

Author information

Author notes

  1. Bruce A. Davis

    Present address: Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, USA

Authors and Affiliations

  1. Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, 231 Bethesda Avenue, 45267-0575, Cincinnati, Ohio, USA

    Bruce A. Davis, Istvan Edes, Ramesh C. Gupta, Ellen F. Young, Hae Won Kim, Nancy A. E. Steenaart, Grazyna Szymanska & Evangelia G. Kranias

Authors
  1. Bruce A. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Istvan Edes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramesh C. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ellen F. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hae Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nancy A. E. Steenaart
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Grazyna Szymanska
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Evangelia G. Kranias
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davis, B.A., Edes, I., Gupta, R.C. et al. The role of phospholamban in the regulation of calcium transport by cardiac sarcoplasmic reticulum. Mol Cell Biochem 99, 83–88 (1990). https://doi.org/10.1007/BF00230337

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00230337

Key words

Search

Navigation