Activators of protein kinase C down-regulate and phosphorylate the T3/T-cell antigen receptor complex of human T lymphocytes.
As judged by indirect immunofluorescence, phorbol 12,13-dibutyrate and 1-oleoyl-2-acetylglycerol induced a rapid, concentration-dependent decrease of about 50% in the surface expression of the T3 antigen on human T lymphoblasts, and of T3 and the T-cell antigen receptor on HPB-ALL cells. Direct binding experiments using 125I-labeled antibody indicated that the reduction in T3 expression corresponded to a decrease in the number of antigen molecules rather than a change in their affinity. Biochemical analyses revealed that phorbol dibutyrate induced a rapid, prominent phosphorylation of the T3 Mr 26,000 gamma chain and to a lesser extent of the Mr 21,000 delta chain. No phosphorylation of the T3 epsilon chain or of the alpha and beta subunits of the T-cell antigen receptor was detected. The data suggest that protein kinase C induces a phosphorylation of the T3 gamma and delta chains that may lead to the down-regulation of the T3/T-cell antigen receptor complex.
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D002451:Cell Compartmentation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D046911:Macromolecular Substances; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D004075:Diglycerides; D046911:Macromolecular Substances; D010703:Phorbol Esters; D011948:Receptors, Antigen, T-Cell; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C