Significance of the membrane protein phospholamban in cyclic AMP-mediated regulation of calcium transport by sarcoplasmic reticulum.
Phospholamban (molecular weight = 22,000), which serves as a regulator of Ca transport ATPase (molecular weight = 100,000) of cardiac sarcoplasmic reticulum (SR), becomes resistant to tryptic digestion upon phosphorylation by cAMP-dependent protein kinase (PK). The protective effect of phosphorylation is accompanied by persistence of the PK-induced stimulation of Ca transport. These findings indicate that structural alteration of phospholamban upon phosphorylation is closely associated with changes in the functional properties of cardiac SR. SR from fast-contracting skeletal muscle of rabbit does not contain a 22,000-dalton substrate for cAMP-dependent PK, nor is Ca transport stimulated by exogenous PK. SR preparation isolated from slow-contracting skeletal muscle of rabbit and dog contains phospholamban, and Ca transport was found to be increased by exogenous cAMP-dependent PK. In view of the distribution of phospholamban among different types of muscle, a hypothesis is presented to explain the relaxation-promoting effects of catecholamines in cardiac and slow-contracting skeletal muscle in which phospholamban is found. This may also account for the absence of a similar effect of catecholamines in fast-contracting skeletal muscle, which does not contain a similar substrate for PK.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology*; D002395:Catecholamines / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D008970:Molecular Weight; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013045:Species Specificity; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D002118:Calcium; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002395:Catecholamines; D000242:Cyclic AMP; D010750:Phosphoproteins; D011494:Protein Kinases; D000099211:Phospholamban