A possible role for protein kinase C activity but not cyclic nucleotide-dependent protein kinases in human natural killer cell lytic activity.
Recent evidence suggests that a Ca++, phospholipid, diacylglycerol-dependent protein kinase, protein kinase C, plays a role in the activation of cytotoxic T lymphocytes by target cells. In this investigation we have examined the role of protein kinase C in human NK cell-mediated cytolysis of K-562 cells. The protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) inhibited human NK cell-mediated cytolysis in a dose dependent manner. On the other hand, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a specific inhibitor of cyclic nucleotide dependent protein kinases had no effect on human NK cell-mediated cytolysis of K562 cells. There is little or no effect on protein synthesis or N-glycosylation activity in human NK cells by H-7. The relative inhibitory ability of the two inhibitors suggest that protein kinase C, acting synergistically with Ca++ mobilization, plays a role in the early stages of human NK cell-mediated cytolysis of K562 target cells.
Hager
C C
CC
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Petroni
K C
KC
Boyce
M A
MA
Forester
L D
LD
Oeltmann
T N
TN
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D000242:Cyclic AMP / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D006031:Glycosylation; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D013449:Sulfonamides
D002121:Calcium Channel Blockers; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium