Phorbol ester-induced phosphorylation of a transmembrane glycoprotein (GP 180) in human blood platelets.
In this study we have used (phorbol-12-O-tetradecanoylphorbol 13-acetate) and its biologically inactive analogue, 4 alpha-phorbol 12,13-didecanoate), to investigate platelet protein phosphorylation with special emphasis on the properties of a membrane protein-cytoskeleton (transmembrane) complex during platelet activation. Our data indicate that phorbol-12-O-tetradecanoylphorbol 13-acetate (but not 4 alpha-phorbol 12,13-didecanoate) induces both a specific platelet shape change and the preferential phosphorylation of a 180-kDa protein (presumably due to the activation of protein kinase C on the cytoplasmic side of the membrane). Further analysis reveals that the 180-kDa protein can be iodinated by lactoperoxidase and is sensitive to trypsin treatment, indicating exposure of this protein on the outer cell surface. The 180-kDa protein has also been found to contain wheat germ agglutinin-binding sites. All evidence indicates that the 180-kDa polypeptide is a transmembrane glycoprotein and, most importantly, that this protein is found to be preferentially accumulated into a specific membrane-cytoskeleton complex during activation via phorbol-12-O-tetradecanoylphorbol 13-acetate treatment. We believe that the observed phosphorylation of this protein may be closely related to the formation of a complex between several membrane proteins and the cytoskeleton during the initial stages of platelet activation.
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins; D010703:Phorbol Esters / Q000494:pharmacology*; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D010750:Phosphoproteins; C030340:elastin microfibril interface located protein; C008876:phorbol-12,13-didecanoate; D013755:Tetradecanoylphorbol Acetate