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, acti...

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Bibliographic Details
Published in:Immunology 1993-08, Vol.79 (4), p.542-547
Main Authors: WHALEN, M. M, DOSHI, R. N, HOMMA, Y, BANKHURST, A. D
Format: Article
Language:English
Subjects:
Analysis of the immune response. Humoral and cellular immunity
Benzoquinones
Biological and medical sciences
Cell Line
Cytotoxicity, Immunologic
Enzyme Activation
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genistein
Humans
Immunobiology
Isoflavones - pharmacology
Killer Cells, Natural - drug effects
Killer Cells, Natural - immunology
Lactams, Macrocyclic
Miscellaneous
Phospholipases - immunology
Phospholipases - metabolism
Phosphorylation
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - metabolism
Quinones - pharmacology
Regulatory factors and their cellular receptors
Rifabutin - analogs & derivatives
Tyrosine - metabolism
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Summary: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.
ISSN:0019-2805
1365-2567