Phospholamban: a regulatory protein of the cardiac sarcoplasmic reticulum.
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.
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*
D009124:Muscle Proteins; D010710:Phosphates; D010750:Phosphoproteins; D011494:Protein Kinases; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D002118:Calcium; D004837:Epinephrine