Role of protein methylation in agonist-induced signal transduction in human platelets.
Possible role of methylation of proteins in platelet activation was examined in this study. Electropermeabilized platelets incorporated radioactivity in the presence of [methyl-3H]-S-adenosylmethionine. Thrombin, PDBu and GTP gamma S increased incorporation of radioactivity in a time-dependent manner. In other experiments, 23 kD membrane proteins incorporated radioactivity in the presence of [methyl-3H]-S-adenosylmethionine and platelet cytosol. Using rap specific antisera the 23 kD methylated proteins were characterized as low Mr G proteins, known as rap1 proteins. N-Acetyl-S-farnesyl-L-cysteine (AFC), an inhibitor of the methyltransferase, inhibited carboxyl methylation of platelet rap1 proteins and also inhibited platelet aggregation and mobilization of cytosolic calcium induced by a variety of agonists in a concentration-dependent manner. Inhibition of methylation of rap1 proteins as well as inhibition of platelet activation by AFC suggests that methylation and consequently translocation of rap1 proteins to plasma membrane may be important for agonist-induced signal transduction in human platelets.
Department of Biological Sciences, Ohio University, Athens 45701.
Huzoor-Akbar
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D020668:rap GTP-Binding Proteins
D001798:Blood Proteins; D007106:Immune Sera; D015240:Phorbol 12,13-Dibutyrate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008780:Methyltransferases; D013917:Thrombin; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; C068268:N-acetyl-S-farnesylcysteine; D002118:Calcium; D000111:Acetylcysteine