title: Phospholamban: a regulatory protein of the cardiac sarcoplasmic reticulum.
abstract: Accelerated calcium transport into the sarcoplasmic reticulum (SR) of the heart may mediate the inotropic actions of agents that act to increase adenosine 3',5'-monophosphate (cyclic AMP) within the cell. Studies in our laboratory have shown that ATP-dependent Ca uptake by cardiac microsomes rich in SR is enhanced by pretreatment with bovine cardiac cyclic AMP-dependent protein kinase (cyclic AMP-PK). Ca2+-activated ATPase is increased concomitantly with Ca uptake, stoichiometric coupling of 2 moles of Ca2+ taken up per mole of ATP hydrolyzed remaining constant. The steady state level of Ca binding is not increased by cyclic AMP-PK pretreatment, suggesting that the turnover rate of the transport system rather than the number of transport sites is increased. Phosphorylation of the SR by protein kinase is half-maximal at approximately 10(-7) M cyclic AMP, a value similar to that which gives half-maximal stimulation of both Ca uptake and Ca2+-activated ATPase. Over 80 percent of the 32P associated with membrane protein is identifiable as phosphoserine and phosphothreonine. The 32P is incorporated into a 22,000-dalton protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein, which we have tentatively named phospholamban (lambda alpha mu beta alpha psi usilon epsilon omega = to receive) appears to particiapte in the regulation of calcium transport by the heart's SR and may play a role in the inotropic actions of drugs, such as epinephrine, which act upon the cyclic AMP-PK system.
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004837:Epinephrine / Q000494:pharmacology; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D010710:Phosphates; D010750:Phosphoproteins; D011494:Protein Kinases; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D002118:Calcium; D004837:Epinephrine