Calcium sequestration in human platelets: is it stimulated by protein kinase C?
Sequestration of calcium into an intracellular storage site is an important mechanism in helping to maintain a low cytoplasmic Ca2+ level in many cells. In platelets, increasing cytoplasmic cAMP lowers the free calcium level in correlation with the phosphorylation of a 22 kD protein. This protein has been thought to enhance uptake of calcium into a platelet membrane bound storage site by activating a calcium-ATPase activity by analogy with phospholamban in cardiac muscle. The evidence for an analogue of phospholamban in platelets is unclear. A pathway involving cAMP dependent kinase also seems unlikely to account for the transience of the calcium signal following agonists in platelets, some of which inhibit the cAMP dependent kinase. Here we discuss the issue of whether activation of protein kinase C, which follows agonist action, leads to enhanced calcium sequestration in platelets and if so, what indications there are for a mechanism. The evidence from our experiments with phorbol myristate acetate treated platelets shows that such an enhancement can be produced by activating protein kinase C. Phosphorylation studies suggest the involvement of a polypeptide or polypeptides distinct from the 22 kD polypeptide. Further work to test this idea is necessary. A brief overview of research on the role of phosphoproteins in calcium regulation in platelets and comparison with their role in cardiac muscle is also presented.
Yoshida
K
K
Department of Legal Medicine, Osaka University School of Medicine, Japan.
Nachmias
V T
VT
D001572:Benzofurans; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D002118:Calcium / Q000097:blood* / Q000378:metabolism; D004789:Enzyme Activation; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D011458:Prostaglandins E / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D001572:Benzofurans; D005456:Fluorescent Dyes; D011458:Prostaglandins E; D012503:Saponins; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2