Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains.
Phosphorylation of the 20,000 molecular weight (MW) light chain of platelet myosin is associated with the activation of platelets and subsequent release of platelet granules, and the protein kinase catalysing this phosphorylation has been identified as the Ca2+/calmodulin-dependent enzyme, myosin light chain kinase. Tumour-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA), which activate Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), can also cause platelet aggregation and phosphorylation of a 20,000-MW peptide in blood platelets. It was therefore of interest to ascertain whether the 20,000-MW peptide phosphorylated in platelets was the light chain of myosin and whether TPA-induced phosphorylation of the 20,000-MW peptide could be differentiated from thrombin-induced phosphorylation. We now report that TPA-induced activation of platelets is associated with the phosphorylation of the 20,000-MW light chain of myosin, that it appears to be mediated mainly through protein kinase C and that the site phosphorylated in the myosin light chain is distinct from that phosphorylated by myosin light chain kinase.
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D009219:Myosin-Light-Chain Kinase; D009218:Myosins / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D046911:Macromolecular Substances; D010704:Phorbols; D011494:Protein Kinases; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D013755:Tetradecanoylphorbol Acetate