Activation of resting human T cells requires prolonged stimulation of protein kinase C.
Purified resting human T cells can be induced to express the alpha subunit of the interleukin 2 receptor and to proliferate by treatment with 12-O-tetradecanoylphorbol-13-acetate plus ionomycin but not with 1,2-dioctanoylglycerol plus ionomycin. Determination of the translocation of protein kinase C showed that 12-O-tetradecanoylphorbol-13-acetate plus ionomycin caused a prolonged membrane association of the enzyme for more than 4 hr, whereas 1,2-dioctanoylglycerol plus ionomycin induced a transient membrane association, which was maximal at 20 min. Delivery of multiple additions of 1,2-dioctanoylglycerol plus ionomycin to the T cells resulted in progressively increased expression of the alpha subunit of the interleukin 2 receptor and proliferation commensurate with the number of multiple additions delivered, suggesting that prolonged protein kinase C activity is required for T-cell activation.
Berry
N
N
Department of Biochemistry, Kobe University School of Medicine, Japan.
Ase
K
K
Kishimoto
A
A
Nishizuka
Y
Y
D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D004075:Diglycerides; D007376:Interleukin-2; C044295:1,2-dioctanoylglycerol; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine