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Gene Review

PLN  -  phospholamban

Canis lupus familiaris

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Disease relevance of PLN


High impact information on PLN


Biological context of PLN

  • The inhibitory effects of PLN 1-31 and PLN 8-47 on the ATPase were reversed by cAMP-dependent phosphorylation of the peptides (Ser16) [8].
  • An acceleration of E2P decomposition upon PLN phosphorylation may contribute to the increased Vmax(Ca) of Ca uptake at 25 degrees C but not at 37 degrees C, based on measurement of the kinetics of E2P decomposition and steady-state E2P formation from Pi at different temperatures [9].
  • Investigators previously, however, have been unsuccessful in demonstrating an effect of PLN phosphorylation or anti-PLN monoclonal antibody (mAb), which is considered to mimic phosphorylation's well-known effect on Km(Ca), on microsomal Ca uptake at the (high) Ca2+ concentrations found intracellularly at peak systole [9].
  • Phospholamban in the reconstituted vesicles was phosphorylated with added catalytic subunit of cAMP-dependent protein kinase to almost the same extent as that in original vesicles [10].
  • The substrate specificity of the purified phosphatase for cardiac phosphoproteins was determined using troponin I, phospholamban, and highly enriched sarcolemmal and sarcoplasmic reticulum preparations, phosphorylated by the cAMP-dependent protein kinase [11].

Anatomical context of PLN

  • Role of leucine 31 of phospholamban in structural and functional interactions with the Ca2+ pump of cardiac sarcoplasmic reticulum [12].
  • Leu(31) of PLB, located at the cytoplasmic membrane boundary, is a critical amino acid shown previously to be essential for Ca(2+)-ATPase inhibition [12].
  • By contrast, the Ca(2+)-pumping activity of skeletal muscle SR, which lacks endogenous PLN, was unaffected [13].
  • METHODS: Ca-uptake and Ca(2+)-ATPase activities in purified phosphorylated and control canine cardiac microsomes, incubated at increasing concentrations of NaOCl or NH2Cl, were related to the extent of PLN phosphorylation by protein kinase A, which was quantitated by PhosphorImager analysis [14].
  • From 1 g cells we typically purified 13.5 mg fusion protein with a PLN content of 2.8 mg [15].

Associations of PLN with chemical compounds

  • Although L31C-PLB failed to cross-link to any Cys or Lys residue of wild-type SERCA2a, L31C did cross-link with high efficiency to T317C of SERCA2a with use of the homobifunctional sulfhydryl cross-linking reagent, 1,6-bismaleimidohexane [12].
  • The ability of two loss-of-function mutants, L31A and L31C, of phospholamban (PLB) to bind to and inhibit the Ca(2+) pump of cardiac sarcoplasmic reticulum (SERCA2a) was investigated using a molecular cross-linking approach [12].
  • No comparable protection against similar oxidative damage of the Ca pump is observed when light fast skeletal muscle microsomes, which lack PLN, are incubated under conditions favorable for phosphorylation nor when PLN's inhibition of the cardiac Ca pump is relieved by proteolytic cleavage of its cytoplasmic domain [14].
  • The specific binding of tannin reverses the inhibition that PLN exerts on cardiac SR ATPase [16].
  • Levels of mRNA encoding beta-myosin heavy chain, mitochondrial creatine kinase, phospholamban, and sarcoplasmic reticulum Ca(2+)-ATPase did not significantly change from baseline, despite development of heart failure [17].

Other interactions of PLN


Analytical, diagnostic and therapeutic context of PLN


  1. The expression of canine cardiac phospholamban in heterologous systems. Cook, E.A., Huggins, J.P., Sathe, G., England, P.J., Piggott, J.R. Biochem. J. (1989) [Pubmed]
  2. Effect of tachycardia on myocardial sarcoplasmic reticulum and Ca2+ dynamics: a mechanism for preconditioning? Domenech, R.J., Sánchez, G., Donoso, P., Parra, V., Macho, P. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  3. Altered sarcoplasmic reticulum Ca2+ ATPase gene expression in congestive heart failure: effect of chronic norepinephrine infusion. Lai, L.P., Raju, V.S., Delehanty, J.M., Yatani, A., Liang, C.S. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  4. Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy. Stabej, P., Leegwater, P.A., Stokhof, A.A., Domanjko-Petric, A., van Oost, B.A. Am. J. Vet. Res. (2005) [Pubmed]
  5. Nature and site of phospholamban regulation of the Ca2+ pump of sarcoplasmic reticulum. James, P., Inui, M., Tada, M., Chiesi, M., Carafoli, E. Nature (1989) [Pubmed]
  6. Complete complementary DNA-derived amino acid sequence of canine cardiac phospholamban. Fujii, J., Ueno, A., Kitano, K., Tanaka, S., Kadoma, M., Tada, M. J. Clin. Invest. (1987) [Pubmed]
  7. Localization of phospholamban in smooth muscle using immunogold electron microscopy. Ferguson, D.G., Young, E.F., Raeymaekers, L., Kranias, E.G. J. Cell Biol. (1988) [Pubmed]
  8. Molecular mechanism of regulation of Ca2+ pump ATPase by phospholamban in cardiac sarcoplasmic reticulum. Effects of synthetic phospholamban peptides on Ca2+ pump ATPase. Sasaki, T., Inui, M., Kimura, Y., Kuzuya, T., Tada, M. J. Biol. Chem. (1992) [Pubmed]
  9. Comparison of the kinetic effects of phospholamban phosphorylation and anti-phospholamban monoclonal antibody on the calcium pump in purified cardiac sarcoplasmic reticulum membranes. Antipenko, A.Y., Spielman, A.I., Sassaroli, M., Kirchberger, M.A. Biochemistry (1997) [Pubmed]
  10. The nature of the modulation of Ca2+ transport as studied by reconstitution of cardiac sarcoplasmic reticulum. Inui, M., Chamberlain, B.K., Saito, A., Fleischer, S. J. Biol. Chem. (1986) [Pubmed]
  11. Purification and characterization of phospholamban phosphatase from cardiac muscle. Kranias, E.G., Steenaart, N.A., Di Salvo, J. J. Biol. Chem. (1988) [Pubmed]
  12. Role of leucine 31 of phospholamban in structural and functional interactions with the Ca2+ pump of cardiac sarcoplasmic reticulum. Chen, Z., Stokes, D.L., Jones, L.R. J. Biol. Chem. (2005) [Pubmed]
  13. Regulation of the calcium ion pump of sarcoplasmic reticulum: reversible inhibition by phospholamban and by the calmodulin binding domain of the plasma membrane calcium ion pump. Vorherr, T., Chiesi, M., Schwaller, R., Carafoli, E. Biochemistry (1992) [Pubmed]
  14. Membrane phosphorylation protects the cardiac sarcoplasmic reticulum Ca(2+)-ATPase against chlorinated oxidants in vitro. Antipenko, A.Y., Kirchberger, M.A. Cardiovasc. Res. (1997) [Pubmed]
  15. Purification of the cardiac sarcoplasmic reticulum membrane protein phospholamban from recombinant Escherichia coli. Krömer, W.J., Carafoli, E., Bailey, J.E. Eur. J. Biochem. (1997) [Pubmed]
  16. Reversal of phospholamban-induced inhibition of cardiac sarcoplasmic reticulum Ca(2+)-ATPase by tannin. Chiesi, M., Schwaller, R. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  17. Endomyocardial gene expression during development of pacing tachycardia-induced heart failure in the dog. Williams, R.E., Kass, D.A., Kawagoe, Y., Pak, P., Tunin, R.S., Shah, R., Hwang, A., Feldman, A.M. Circ. Res. (1994) [Pubmed]
  18. Immunoelectron microscopical localization of phospholamban in adult canine ventricular muscle. Jorgensen, A.O., Jones, L.R. J. Cell Biol. (1987) [Pubmed]
  19. Sequence analysis of phospholamban. Identification of phosphorylation sites and two major structural domains. Simmerman, H.K., Collins, J.H., Theibert, J.L., Wegener, A.D., Jones, L.R. J. Biol. Chem. (1986) [Pubmed]
  20. Purified, reconstituted cardiac Ca2+-ATPase is regulated by phospholamban but not by direct phosphorylation with Ca2+/calmodulin-dependent protein kinase. Reddy, L.G., Jones, L.R., Pace, R.C., Stokes, D.L. J. Biol. Chem. (1996) [Pubmed]
  21. Localization of phospholamban in slow but not fast canine skeletal muscle fibers. An immunocytochemical and biochemical study. Jorgensen, A.O., Jones, L.R. J. Biol. Chem. (1986) [Pubmed]
  22. Biochemical and biophysical comparison of native and chemically synthesized phospholamban and a monomeric phospholamban analog. Mayer, E.J., McKenna, E., Garsky, V.M., Burke, C.J., Mach, H., Middaugh, C.R., Sardana, M., Smith, J.S., Johnson, R.G. J. Biol. Chem. (1996) [Pubmed]
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