Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 442)
Phospholemman: A Cardiac Taurine Channel Involved in Regulation of Cell Volume
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:
E1APQEHDPFTYEYQSLR I 18 GGLIIAGILFILGILIVLS 37 RRCRCKFNQQQRTGEPDEEE GTFR S 62 SIRRLS 68 TRRR72
KeywordsXenopus 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.
- 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
- 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
- 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
- 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
- 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.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
© Springer Science+Business Media New York 1998