Human T cell activation by phorbol esters and diacylglycerol analogues.
Activation of protein kinase C (PKC), by the phorbol ester PMA, or the membrane-permeable diacylglycerol 1-oleoyl 2-acetylglycerol (OAG), had different effects on the proliferation-associated responses of a more than 99% pure population of human T cells. Treatment with PMA or OAG caused down-regulation of the TCR-CD3 complex, but only PMA, in combination with ionomycin, was capable of stimulating IL-2R expression and proliferation. Immunocytochemical staining with antisera specific for the PKC subspecies alpha, beta I, beta II, and gamma showed that untreated resting T cells normally coexpress alpha, beta I, and beta II PKC subspecies, which are distributed diffusely throughout the cell, with some localization around the periphery of the nucleus. There was no difference between the responses of these PKC subspecies to OAG and PMA, redistributing, after 10 min of treatment, to a discrete focal area within the cell. Treatment with OAG resulted in transient redistribution of PKC, maximal at 10 min, while in PMA-stimulated cells, the PKC redistribution was prolonged, persisting for at least 24 h. The results suggest that the difference in cellular response to treatment with PMA and OAG is not a consequence of differential activation of various PKC subspecies.
Berry
N
N
Department of Biochemistry, Kobe University School of Medicine, Japan.
Ase
K
K
Kikkawa
U
U
Kishimoto
A
A
Nishizuka
Y
Y
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D002469:Cell Separation; D004075:Diglycerides / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000187:drug effects*; D010641:Phenotype; D011493:Protein Kinase C / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000145:classification / Q000201:enzymology / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004075:Diglycerides; D005989:Glycerides; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate