Phospholipase C activation in the cytotoxic response of human natural killer cells requires protein-tyrosine kinase activity.
Treatment of highly purified natural killer (NK) cells with the protein-tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, diminished their ability to lyse K562 target cells by as much as 100%. The ability of NK cells to bind to K562 cells was not affected by PTK inhibition. However, activation of phospholipase C (PLC) in response to K562 cell binding (as measured by inositol phosphate turnover) was decreased by as much as 75% when PTK activity was inhibited. Furthermore, there was an increase in tyrosine phosphorylation of NK cell PLC gamma 2 after exposure to K562 target cells. These data indicate that a PTK is involved in the activation of NK PLC by tumour target cells in the cytotoxic response.
Whalen
M M
MM
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131.
Doshi
R N
RN
Homma
Y
Y
Bankhurst
A D
AD
D016227:Benzoquinones; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D047029:Lactams, Macrocyclic; D010740:Phospholipases / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D014443:Tyrosine / Q000378:metabolism
D016227:Benzoquinones; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010740:Phospholipases