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 protei n-tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, dimini shed their ability to lyse K562 target cells by as much as 100%. The a bility of NK cells to bind to K562 cells was not affected by PTK inhib ition. However, activation of phospholipase C (PLC) in response to K56 2 cell binding (as measured by inositol phosphate turnover) was decrea sed by as much as 75% when PTK activity was inhibited. Furthermore, th ere was an increase in tyrosine phosphorylation of NK cell PLCgamma2 a fter 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 cyt otoxic response.