Regulation of human platelet membrane Ca2+ transport by cAMP- and calmodulin-dependent phosphorylation.
We have examined the effects of added cAMP-dependent protein kinase and endogenous calmodulin-dependent kinase on Ca2+ transport in purified internal membranes from human platelets. Both Ca2+ uptake and Ca2+-ATPase activity were maximally stimulated about 2-fold by addition of cAMP-dependent protein kinase. Cyclic AMP-dependent protein kinase inhibitor reduced both Ca2+ uptake and Ca2+-ATPase activities at concentrations which also inhibited cAMP-dependent protein phosphorylation. In addition, concerted stimulation of Ca2+-ATPase by exogenous calmodulin and added catalytic subunit of cAMP-dependent protein kinase was observed. A 22-kDa protein was phosphorylated by both cAMP-dependent and calmodulin-dependent kinases at the same rate as stimulation of the Ca2+-ATPase. Cyclic AMP-dependent phosphorylation of the 22-kDa polypeptide was inhibited by the protein kinase inhibitor and calmodulin-dependent phosphorylation was inhibited by chlorpromazine and EGTA. These results are consistent with the hypothesis that one mode of control of Ca2+ homeostasis in platelets may be similar to the phospholamban system in cardiac muscle.
D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000097:blood*; D002147:Calmodulin / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D010766:Phosphorylation; D011494:Protein Kinases / Q000097:blood*
D002147:Calmodulin; D046911:Macromolecular Substances; D011494:Protein Kinases; D000252:Calcium-Transporting ATPases; D002118:Calcium