PLN phosphorylation signalling

PLN phosphorylation signalling - key publications using PLN antibodies

Please rate these pages to support our infographic project:
Get free premium widgets for your blog and website.

chemical molecules diagram

Image: Interactive infographic – click on selected pathway arrows to reveal key publications for each area.

Review article - The Role of Phospho-ser-16-Phospholamban in Cardiac Physiology

Cardiovascular disease is the single most prevalent cause of death in the United States and Europe. As such, research investigating the pathophysiology of the various forms of heart disease garners billions of dollars of research funding each year. An essential component of this research is focused on the molecular basis of normal heart function. Key to understanding these molecular mechanisms is phospholamban (PLN), an important regulatory protein that embeds within the membrane of the cardiomyocyte sarcoplasmic reticulum (SR). PLN plays a central role in calcium regulation and cardiac relaxation and as such, is a molecule that is deserving of attention and further understanding.  Read full article.

  1. Baltas, L.G. et al. 1997a. The endogenous cardiac sarcoplasmic reticulum Ca2+/calmodulin-dependent kinase is activated in response to β-adrenergic stimulation and becomes Ca2+-independent in intact beating hearts. FEBS Letters. 409(2), pp.131-136.
  2. Baltas, L.G. et al. 1997b. Effects of zinc on phospholamban phosphorylation. Biochem Biophys Res Commun. 232(2), pp.394-7.
  3. Baltas, L.G. et al. 1997c. Effects of zinc on phospholamban phosphorylation. Biochemical and Biophysical Research Communications. 232(2), pp.394-397.
  4. Bartel, S. et al. 2003. New insights into beta(2)-adrenoceptor signaling in the adult rat heart. Cardiovascular Research. 57(3), pp.694-703.
  5. Bartel, S. et al. 2000. Phosphorylation of phospholamban at threonine-17 in the absence and presence of beta-adrenergic stimulation in neonatal rat cardiomyocytes. Journal of Molecular and Cellular Cardiology. 32(12), pp.2173-2185.
  6. Bhupathy, P. et al. 2009. Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes. Journal of Molecular and Cellular Cardiology. 47(5), pp.723-729.
  7. Boknik, P. et al. 2000a. Protein phosphatase activity is increased in a rat model of long-term beta-adrenergic stimulation. Naunyn-Schmiedebergs Archives of Pharmacology. 362(3), pp.222-231.
  8. Boknik, P. et al. 2000b. Protein phosphatase activity is increased in a rat model of long-term beta-adrenergic stimulation. Naunyn Schmiedebergs Arch Pharmacol. 362(3), pp.222-31.
  9. Boknik, P. et al. 2001a. Enhanced protein phosphorylation in hypertensive hypertrophy. Cardiovascular Research. 51(4), pp.717-728.
  10. Boknik, P. et al. 2001b. Role of protein phosphatases in regulation of cardiac inotropy and relaxation. American Journal of Physiology-Heart and Circulatory Physiology. 280(2), pp.H786-H794.
  11. Boknik, P. et al. 2001c. Role of protein phosphatases in regulation of cardiac inotropy and relaxation. Am J Physiol Heart Circ Physiol. 280(2), pp.H786-94.
  12. Boknik, P. et al. 1999. Regional expression of phospholamban in the human heart. Cardiovascular Research. 43(1), pp.67-76.
  13. Brixius, K. et al. 2003. Ser16-, but not Thr17-phosohorylation of phospholamban influences frequency-dependent force generation in human myocardium. European Heart Journal. 24, pp.16-16.
  14. Calaghan, S. et al. 1998a. Preservation of the in vivo phosphorylation status of phospholamban in the heart: Evidence for a site-specific difference in the dephosphorylation of phospholamban. Biochemical and Biophysical Research Communications. 248(3), pp.701-705.
  15. Calaghan, S.C. et al. 1998b. Co-ordinated changes in cAMP, phosphorylated phospholamban, Ca2+ and contraction following beta-adrenergic stimulation of rat heart. Pflugers Archiv-European Journal of Physiology. 436(6), pp.948-956.
  16. Catalucci, D. et al. 2009. At Increases Sarcoplasmic Reticulum Ca2+ Cycling by Direct Phosphorylation of Phospholamban at Thr(17). Journal of Biological Chemistry. 284(41), pp.28180-28187.
  17. Cerra, M.C. and Imbrogno, S. 2012. Phospholamban and cardiac function: a comparative perspective in vertebrates. Acta Physiologica. 205(1), pp.9-25.
  18. Cha, H. et al. 2008. PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility. Journal of Molecular and Cellular Cardiology. 45(6), pp.796-803.
  19. Colyer, J. 1998. Phosphorylation states of phospholamban. Cardiac Sarcoplasmic Reticulum Function and Regulation of Contractility. 853, pp.79-91.
  20. Colyer, J. 2009. Analyzing Protein Phosphorylation. Protein Protocols Handbook, Third Edition. pp.1547-1553.
  21. Colyer, J. 2014. Agents for and method of quantifying binding. Google Patents. Available from:
  22. Currie, S. and Smith, G.L. 1999. Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure. Cardiovascular Research. 41(1), pp.135-146.
  23. Czernik, A. et al. 1997. Phosphorylation State-Specific Antibodies. In: Hemmings, H., Jr. ed. Regulatory Protein Modification.   Humana Press, pp.219-250.
  24. El-Armouche, A. et al. 2006. Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes. Biochemical and Biophysical Research Communications. 346(3), pp.700-706.
  25. Freire, P.P. et al. 2014. Obesity does not lead to imbalance between myocardial phospholamban phosphorylation and dephosphorylation. Arq Bras Cardiol. 103(1), pp.41-50.
  26. Gao, M.H. et al. 2008. Adenylyl Cyclase Type VI Increases Akt Activity and Phospholamban Phosphorylation in Cardiac Myocytes. Journal of Biological Chemistry. 283(48), pp.33527-33535.
  27. Gergs, U. et al. 2009. Phosphorylation of phospholamban and troponin I through 5-HT4 receptors in the isolated human atrium. Naunyn-Schmiedebergs Archives of Pharmacology. 379(4), pp.349-359.
  28. Gombosova, I. et al. 1998. Postnatal changes in contractile time parameters, calcium regulatory proteins, and phosphatases. American Journal of Physiology-Heart and Circulatory Physiology. 274(6), pp.H2123-H2132.
  29. Hagemann, D. et al. 2000a. Frequency-encoding Thr17 phospholamban phosphorylation is independent of Ser16 phosphorylation in cardiac myocytes. J Biol Chem. 275(29), pp.22532-6.
  30. Hagemann, D. et al. 2000b. Frequency-encoding Thr(17) phospholamban phosphorylation is independent of Ser(16) phosphorylation in cardiac myocytes. Journal of Biological Chemistry. 275(29), pp.22532-22536.
  31. Hagemann, D. and Xiao, R.P. 2002. Dual site phospholamban phosphorylation and its physiological relevance in the heart. Trends Cardiovasc Med. 12(2), pp.51-6.
  32. Haworth, R.S. et al. 2011. Regulation by phosphodiesterase isoforms of protein kinase A-mediated attenuation of myocardial protein kinase D activation. Basic Research in Cardiology. 106(1), pp.51-63.
  33. Huke, S. and Bers, D.M. 2007. Temporal dissociation of frequency-dependent acceleration of relaxation and protein phosphorylation by CaMKII. J Mol Cell Cardiol. 42(3), pp.590-9.
  34. Huke, S. and Bers, D.M. 2008. Ryanodine receptor phosphorylation at Serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications. 376(1), pp.80-85.
  35. Inagaki, M. et al. 1997. Phosphorylation-dependent control of structures of intermediate filaments: a novel approach using site- and phosphorylation state-specific antibodies. J Biochem. 121(3), pp.407-14.
  36. Jiang, M. et al. 2004. Coordinate downregulation of CaM kinase II and phospholamban accompanies contractile phenotype transition in the hyperthyroid rabbit soleus. American Journal of Physiology-Cell Physiology. 287(3), pp.C622-C632.
  37. Kaasik, A. et al. 2001. Decreased expression of phospholamban is not associated with lower beta-adrenergic activation in rat atria. Mol Cell Biochem. 223(1-2), pp.109-15.
  38. Kaumann, A.J. et al. 1996. Beta 2-adrenoceptor activation by zinterol causes protein phosphorylation, contractile effects and relaxant effects through a cAMP pathway in human atrium. Mol Cell Biochem. 163-164, pp.113-23.
  39. Kirchhefer, U. et al. 2005. Enhanced cardiac function in mice overexpressing protein phosphatase inhibitor-2. Cardiovascular Research. 68(1), pp.98-108.
  40. Kuschel, M. et al. 1999a. Ser(16) prevails over Thr(17) phospholamban phosphorylation in the beta-adrenergic regulation of cardiac relaxation. American Journal of Physiology-Heart and Circulatory Physiology. 276(5), pp.H1625-H1633.
  41. Kuschel, M. et al. 1999b. Gi Protein-mediated Functional Compartmentalization of Cardiac β2-Adrenergic Signaling. Journal of Biological Chemistry. 274(31), pp.22048-22052.
  42. Kuschel, M. et al. 1999c. beta(2)-adrenergic cAMP signaling is uncoupled from phosphorylation of cytoplasmic proteins in canine heart. Circulation. 99(18), pp.2458-2465.
  43. Larsen, K.O. et al. 2008. Diastolic dysfunction in alveolar hypoxia: a role for interleukin-18-mediated increase in protein phosphatase 2A. Cardiovascular Research. 80(1), pp.47-54.
  44. Larsen, K.O. et al. 2006. Alveolar hypoxia induces left ventricular diastolic dysfunction and reduces phosphorylation of phospholamban in mice. American Journal of Physiology-Heart and Circulatory Physiology. 291(2), pp.H507-H516.
  45. Li, B.L. et al. 2006. Signaling pathways regulating murine cardiac CREB phosphorylation. Biochemical and Biophysical Research Communications. 350(1), pp.179-184.
  46. Liu, S. et al. 2012. Phosphodiesterases coordinate cAMP propagation induced by two stimulatory G protein-coupled receptors in hearts. Proc Natl Acad Sci U S A. 109(17), pp.6578-83.
  47. Mattiazzi, A. et al. 2005. Role of phospholamban phosphorylation on Thr(17) in cardiac physiological and pathological conditions. Cardiovascular Research. 68(3), pp.366-375.
  48. Mayer, E.J. et al. 2000. Characterization and quantitation of phospholamban and its phosphorylation state using antibodies. Biochemical and Biophysical Research Communications. 267(1), pp.40-48.
  49. Medeiros, A. et al. 2008. Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice. Journal of Applied Physiology. 104(1), pp.103-109.
  50. Munch, G. et al. 2000. SERCA2a activity correlates with the force-frequency relationship in human myocardium. American Journal of Physiology-Heart and Circulatory Physiology. 278(6), pp.H1924-H1932.
  51. Mundina-Weilenmann, C. et al. 1996. Immunodetection of phosphorylation sites gives new insights into the mechanisms underlying phospholamban phosphorylation in the intact heart. J Biol Chem. 271(52), pp.33561-7.
  52. Mundina-Weilenmann, C. et al. 2000. Endoplasmic reticulum contribution to the relaxant effect of cGMP- and cAMP-elevating agents in feline aorta. American Journal of Physiology-Heart and Circulatory Physiology. 278(6), pp.H1856-H1865.
  53. Ng, J. and Cantrell, D. 1997. STAT3 is a serine kinase target in T lymphocytes. Interleukin 2 and T cell antigen receptor signals converge upon serine 727. J Biol Chem. 272(39), pp.24542-9.
  54. Prasad, V. et al. 2008. Impaired Cardiac Contractility in Mice Lacking Both the AE3 Cl-/HCO3- Exchanger and the NKCC1 Na+-K+-2Cl(-) Cotransporter EFFECTS ON Ca2+ HANDLING AND PROTEIN PHOSPHATASES. Journal of Biological Chemistry. 283(46), pp.31303-31314.
  55. Rodriguez, P. et al. 2007. Phosphorylation of human inhibitor-1 at Ser67 and/or Thr75 attenuates stimulatory effects of protein kinase A signaling in cardiac myocytes. Am J Physiol Heart Circ Physiol. 293(1), pp.H762-9.
  56. Rolim, N.P.L. et al. 2007. Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure. Physiological Genomics. 29(3), pp.246-252.
  57. Roof, S.R. et al. 2011. Effects of increased systolic Ca(2)(+) and phospholamban phosphorylation during beta-adrenergic stimulation on Ca(2)(+) transient kinetics in cardiac myocytes. Am J Physiol Heart Circ Physiol. 301(4), pp.H1570-8.
  58. Simmerman, H.K.B. and Jones, L.R. 1998. Phospholamban: Protein structure, mechanism of action, and role in cardiac function. Physiological Reviews. 78(4), pp.921-947.
  59. Singh, P. et al. 2009. Alpha-kinase anchoring protein alphaKAP interacts with SERCA2A to spatially position Ca2+/calmodulin-dependent protein kinase II and modulate phospholamban phosphorylation. J Biol Chem. 284(41), pp.28212-21.
  60. Snabaitis, A.K. et al. 2006. A novel role for protein phosphatase 2A in receptor-mediated regulation of the cardiac sarcolemmal Na+/H+ exchanger NHE1. Journal of Biological Chemistry. 281(29), pp.20252-20262.
  61. Sulakhe, P.V. and Vo, X.T. 1995. Regulation of phospholamban and troponin-I phosphorylation in the intact rat cardiomyocytes by adrenergic and cholinergic stimuli: roles of cyclic nucleotides, calcium, protein kinases and phosphatases and depolarization. Mol Cell Biochem. 149-150, pp.103-26.
  62. Sulakhe, P.V. et al. 1997. Protein phosphorylation in rat cardiac microsomes: effects of inhibitors of protein kinase A and of phosphatases. Mol Cell Biochem. 175(1-2), pp.109-15.
  63. Tschope, C. et al. 2004. Improvement of defective sarcoplasmic reticulum Ca2+ transport in diabetic heart of transgenic rats expressing the human kallikrein-1 gene. Faseb j. 18(15), pp.1967-9.
  64. Valverde, C.A. et al. 2005. Frequency-dependent acceleration of relaxation in mammalian heart: a property not relying on phospholamban and SERCA2a phosphorylation. J Physiol. 562(Pt 3), pp.801-13.
  65. Valverde, C.A. et al. 2006. Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart. Cardiovascular Research. 70(2), pp.335-345.
  66. Vasanji, Z. et al. 2006. Alterations in cardiac contractile performance and sarcoplasmic reticulum function in sucrose-fed rats is associated with insulin resistance. American Journal of Physiology-Cell Physiology. 291(4), pp.C772-C780.
  67. Wanichawan, P. et al. 2011. Full-length cardiac Na+/Ca2+ exchanger 1 protein is not phosphorylated by protein kinase A. Am J Physiol Cell Physiol. 300(5), pp.C989-97.
  68. Xu, X.D. et al. 2005. ASF/SF2-Regulated CaMKII delta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Cell. 120(1), pp.59-72.
  69. Yamada, M. et al. 2006. Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates heart failure progression in genetic cardiomyopathy. Faseb Journal. 20(8), pp.1197-+.
  70. Zhang, R. et al. 2005. Calmodulin kinase II inhibition protects against structural heart disease. Nature Medicine. 11(4), pp.409-417.
  71. Zhao, W. et al. 2004. Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility. Journal of Molecular and Cellular Cardiology. 37(2), pp.607-612.
  72. Zhao, X.Y. et al. 2008. rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca2+-ATPase activity and cardiac dysfunction in rats with myocardial infarction. European Journal of Heart Failure. 10(1), pp.47-54.
  73. Zhou, X.W. et al. 2007. Proteomic. studies of PP2A-B56 gamma 1 phosphatase complexes reveal phosphorylation-regulated partners in cardiac local signaling. Journal of Proteome Research. 6(9), pp.3433-3442.

Back to main infographic.

About us
meet the team
Badrilla is a manufacturer of outstanding antibodies against cardiac proteins and phospho-proteins, and the manufacturer of leading kits for the study of protein S-palmitoylation.

Follow us on social

Contact us
We look forward to providing your favourite antibodies and kits
gender and body