Rapid modulation of tumor necrosis factor membrane receptors by activators of protein kinase C.
Tumor necrosis factor membrane receptors are rapidly down-regulated upon treatment of activated T lymphocytes with various activators of protein kinase C. Loss of binding-capacity was half maximal after 2 min. incubation in 10 ng/ml of phorbol 12-myristate 13-acetate. A similar modulation could be induced with either the calcium ionophore A 23187 or the protein kinase C activator 1-oleyl-2-acetyl glycerol, whereas 1,2-diolein and dibutyryl cAMP were ineffective. Protein kinase C inhibitor H7 antagonizes the phorbol ester-induced TNF receptor modulation. These data suggest an important role of protein kinase C in the control of TNF responsiveness by regulation of TNF binding-capacity possibly via direct phosphorylation of specific receptor proteins.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008213:Lymphocyte Activation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha
D004075:Diglycerides; D006023:Glycoproteins; D007546:Isoquinolines; D010879:Piperazines; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate