Taurine 3 pp 219-228 | Cite as

Phospholemman: A Cardiac Taurine Channel Involved in Regulation of Cell Volume

  • J. Randall Moorman
  • Larry R. Jones
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 442)


The story begins with the study of purified plasma membrane vesicles from canine heart10,11. Phosphorylation assays showed that these vesicles contained endogenous PK-A16 and PK-C24 activities. PK-A phosphorylated several proteins in cardiac SL vesicles, the major one of which migrated with an apparent Mr=15,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). PK-C, in contrast, phosphorylated only one substrate in cardiac SL vesicles, also of Mr=15,00016,24. Based on these results, this major SL protein substrate of PK-A and PK-C was provisionally named the “15-kDa protein.” Phosphorylation by PK-A and PK-C was additive, suggesting that at least two different sites of the protein were phosphorylated. In rodent hearts perfused with β-adrenergic23 and α1-adrenergic15 agonists, the “15-kDa protein” was again the major SL substrate phosphorylated, and 32P-labeling of the protein in actively contracting myocardium correlated with the positive inotropic response induced by either agonist. Thus, results with intact myocardial tissue strongly supported a functional role for “15-kDa protein” phosphorylation by PK-A and PK-C. Phosphorylation of the “15-kDa protein” in cardiac membrane preparations and in intact cells was confirmed in other laboratories12,17,18,26. The protein was purified, cloned, and sequenced22, and was named PHOSPHOLEMMAN (PLM). This name denotes the protein’s location within the plasma membrane and its characteristic multisite phosphorylation. The mature protein (that present in SL vesicles) contained only 72 amino acids (Fig. 1), whose sequence is as follows:



Xenopus Oocyte Regulatory Volume Decrease Anion Current Positive Inotropic Response Membrane Phosphoprotein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Attali, B., Latter, H., Rachamim, N., and Garty, H, 1995, A corticosteroid-induced gene expressing an “IsK-like” K+ channel activity in Xenopus oocytes, Proc. Natl. Acad. Sci., 92:6092–6096.PubMedCrossRefGoogle Scholar
  2. 2.
    Boulanger-Saunier, C., Kattenberg, D.M., Stoclet, J., 1985, Cyclic AMP-dependent phosphorylation of a 16-kDa protein in a plasma membrane-enriched fraction of rat aortic myocytes, Febs Lett, 193:283–288.PubMedCrossRefGoogle Scholar
  3. 3.
    Boulanger-Saunier, C. and Stoclet, J., 1987, A 16-kDa protein substrate for protein kinase C and its phosphorylation upon stimulation of vasopressin receptors in rat aortic myocytes, Biochem. Biophys. Res. Comm.,143:517–524.PubMedCrossRefGoogle Scholar
  4. 4.
    Cooper, R.H., Kobayashi, K., and Williamson, J.R., 1984, Phosphorylation of a 16-kDa protein by diacylglycerol-activated protein kinase C in vitro and by vasopressin in intact hepatocytes, Febs Lett, 166:125–130.PubMedCrossRefGoogle Scholar
  5. 5.
    Crowe, W. E., J. Altamirano, L. Huerto, and F. J. Alvarez-Leefmans. 1995. Volume changes in single N1E-115 neuroblastoma cells measured with a fluorescent probe. Neuroscience, 69:283–296.PubMedCrossRefGoogle Scholar
  6. 6.
    Fu, X. and Kamps, M.P., 1997, E2a-Pbx1 induces aberrant expression of tissue-specific and developmentally regulated genes when expressed in NIH3T3 fibroblasts, Mol. Cell. Biol., 17Google Scholar
  7. 7.
    Huxtable, R. J., 1992, Physiological actions of taurine, Physiol. Rev., 72:101–163.PubMedGoogle Scholar
  8. 8.
    Jackson, P.S. and Strange, K., 1993, Volume-sensitive anion channels mediate swelling-activated inositol and taurine efflux, Am. J. Physiol., 265:C1489–C1500.PubMedGoogle Scholar
  9. 9.
    Jackson, P.S. and Strange, K., 1995, Characterization of the voltage-dependent properties of a volume-sensitive anion conductance, J. Gen. Physiol., 105:661–677.PubMedCrossRefGoogle Scholar
  10. 10.
    Jones, L.R., 1988, Rapid preparation of canine cardiac sarcolemmal vesicles by sucrose flotation, Methods Enzymol., 157:85–91.PubMedCrossRefGoogle Scholar
  11. 11.
    Jones, L.R., Besch, H.R., Jr., Fleming, J.W., McConnaughey, M.M., and Watanabe, A.M., 1979, Separation of vesicles of cardiac sarcolemma from vesicles of cardiac sarcoplasmic reticulum: Comparative biochemical analysis of component activities, J. Biol. Chem., 254:530–539.PubMedGoogle Scholar
  12. 12.
    Karczewski, P., Bartel, S., and Krause, E.-G., 1990, Differential sensitivity to isoprenaline of troponin I and phospholamban phosphorylation in isolated rat hearts. Biochem. J., 266:115–122.PubMedGoogle Scholar
  13. 13.
    Kowdley, G. C., Ackerman, S.J., Chen, Z., Szabo, G., Jones, L.R., and Moorman, J.R., 1997, Anion, cation, and zwitterion-selectivity of phospholemman channel molecules, Biophys. J., 72:141–145.PubMedCrossRefGoogle Scholar
  14. 14.
    Kowdley, G. C., Ackerman, S.J., John, J.E., Jones, L.R., and Moorman, J.R., 1994, Hyperpolarization-activated chloride currents in Xenopus oocytes, J. Gen. Physiol., 103:217–230.PubMedCrossRefGoogle Scholar
  15. 15.
    Lindemann, J.P., 1985, α-Adrenergic stimulation of sarcolemmal protein phosphorylation and slow responses in intact myocardium, J. Biol. Chem., 261:4860–4867.Google Scholar
  16. 16.
    Manalan, A.S. and Jones, L.R., 1982, Characterization of the intrinsic cAMP-dependent protein kinase activity and endogenous substrates in highly purified cardiac sarcolemmal vesicles, J. Biol. Chem., 257:10052–10062.PubMedGoogle Scholar
  17. 17.
    Meij, J.T., Bezstarosti, A.K., Panagia, V., and Lamers, J.M.J., 1991, Phorbol ester and the actions of phosphatidylinositol 4, 5-bisphosphate specific phospholipase C and protein kinase C in microsomes prepared from cultured cardiomyocytes, Mol. Cell. Biochem., 105:37–47.PubMedCrossRefGoogle Scholar
  18. 18.
    Miyakoda, G., Yoshida, A., Takisawa, H., and Nakamura, T., 1987, β-adrenergic regulation of contractility and protein phosphorylation in spontaneously beating isolated rat myocardial cells, J. Biochem., 102:211–224.PubMedGoogle Scholar
  19. 19.
    Moorman, J.R., Ackerman, S.J., Kowdley, G.C., Griffin, M.P., Mounsey, J.P., Chen, Z., Cala, S.E., O’Brian, J.J., Szabo, G., and Jones, L.R., 1995, Unitary anion currents through phospholemman channel molecules, Nature, 377:737–740.PubMedCrossRefGoogle Scholar
  20. 20.
    Moorman, J.R., Palmer, C.J., John, J.E., Durieux, M.E., and Jones, L.R., 1992, Phospholemman expression induces a hyperpolarization-activated chloride current in Xenopus oocytes, J. Biol. Chem., 267:14551–14554.PubMedGoogle Scholar
  21. 21.
    Morrison, B.W. and Leder, P., 1994, neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors. Oncogene, 9:3417–3426.PubMedGoogle Scholar
  22. 22.
    Palmer, C. J., Scott, B.T., and Jones, L.R., 1991, Purification and complete sequence determination of the major plasma membrane substrate for cAMP-dependent protein kinase and protein kinase C in myocardium, J. Biol. Chem., 266:11126–11130.PubMedGoogle Scholar
  23. 23.
    Presti, C.F., Jones, L.R., and Lindemann, J.P., 1985, Isoproterenol-induced phosphorylation of a 15-kilodalton sarcolemmal protein in intact myocardium, J. Biol. Chem., 260:3860–3867.PubMedGoogle Scholar
  24. 24.
    Presti, C.F., Scott, B.T., and Jones, L.R., 1985, Identification of an endogenous protein kinase C activity and its intrinsic 15-kilodalton substrate in purified canine cardiac sarcolemmal vesicles, J. Biol. Chem., 260:13879–13889.PubMedGoogle Scholar
  25. 25.
    Szucs, G., Heinke, S., De Greef, C., Raeymaekers, L., Eggermont, J., Droogmans, G., and Nilius, B., 1996, The volume-activated chloride current in endothelial cells from bovine pulmonary artery is not modulated by phosphorylation, Pflugers Archiv. — European. Journal of Physiology, 431:540–548.PubMedCrossRefGoogle Scholar
  26. 26.
    Talosi, L. and Kranias, E.G., 1992, Effect of a-adrenergic stimulation on activation of protein kinase C and phosphorylation of proteins in intact rabbit hearts, Circ. Res., 70:670–678.PubMedCrossRefGoogle Scholar
  27. 27.
    Voets, T., Szucs, G., Droogmans, G., and Nilius, B., 1995, Blockers of volume-activated Cl-currents inhibit endothelial cell proliferation, Pflugers Archiv. — European. Journal of Physiology, 431:132–134.PubMedCrossRefGoogle Scholar
  28. 28.
    Walaas, S.I., Czernik, A.J., Olstad, O.K., Sletten, K., and Walaas, O., 1994, Protein kinase C and cyclic AMP-dependent protein kinase phosphorylate phospholemman, an insulin and adrenaline-regulated membrane phosphoprotein, at specific sites in the carboxy terminal domain, Biochem. J., 304:635–640.PubMedGoogle Scholar
  29. 29.
    Walaas, S.I., Horn, R.S., Albert, K.A., Adler, A., and Walaas, A., 1988, Phosphorylation of multiple sites in a 15,000 dalton proteolipid from rat skeletal muscle sarcolemma, catalyzed by adenosine 3′, 5′-monophosphate-dependent and calcium/phospholipid-dependent protein kinases, Biochimica et Biophysica Acta, 968:127–137.PubMedCrossRefGoogle Scholar
  30. 30.
    Wald, H., Goldstein, O., Asher, C., Yagil, Y., and Garty, H., 1996, Aldosterone induction and epithelial distribution of CHIF, Am. J. Physiol., 271:F322–9.PubMedGoogle Scholar
  31. 31.
    Widmaier, E.P., Osawa, S., and Hall, P.F., 1986, Phosphorylation of three proteins in the plasma membrane of Y-1 adrenal cells by a membrane-bound adenosine 3′, 5′-monophosphate-dependent protein kinase, Endocrinology, 118:701–708.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • J. Randall Moorman
    • 1
  • Larry R. Jones
    • 2
  1. 1.University of VirginiaCharlottesvilleUSA
  2. 2.Indiana University School of MedicineIndianapolisUSA

Personalised recommendations