The role of phorbol ester-sensitive protein kinase C isoforms in lymphokine-activated killer cell-mediated cytotoxicity: dissociation between perforin-dependent and Fas-dependent cytotoxicity.
Treatment of lymphokine-activated killer (LAK) cells with phorbol ester (PMA) caused the downmodulation of LAK activity concomitantly with the inhibition of serine esterase (SE) release, which has been shown as a marker for perforin-dependent cell-mediated cytotoxicity. The reduction of perforin-dependent LAK activity by PMA-treatment appeared to be due to the disappearance of PMA-sensitive protein kinase C (PKC) isoforms such as PKC alpha, gamma, epsilon, theta. In contrast, Fas-mediated LAK activity was refractory against PMA-induced downregulation. Treatment of LAK cells with PMA caused a disappearance of cytotoxicity against Fas L5178Y tumor cells, while cytotoxicity against Fas+ transfectants was not affected by PMA treatment. Moreover, Fas-mediated LAK activity of perforin-knockout mice was not inhibited by PMA treatment. These results clearly demonstrated that Fas-mediated cytotoxicity could be dissociated from perforin-mediated cytotoxicity by their different requirement of PMA-sensitive PKC isoforms.
Ohmi
Y
Y
Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Ohta
A
A
Sasakura
Y
Y
Sato
N
N
Yahata
T
T
Santa
K
K
Habu
S
S
Nishimura
T
T
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004950:Esterases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D007940:Leukemia L5178; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D007527:Isoenzymes; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D019014:fas Receptor; D054353:Perforin; C497256:Prkce protein, mouse; C087857:protein kinase C gamma; C496630:Prkca protein, mouse; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D004950:Esterases; C022635:serine esterase; D013755:Tetradecanoylphorbol Acetate