Activation of Protein Kinase D is part of the NK cell signaling pathway activated in the tumor‐cell destroying process

Natural killer (NK) cells are lymphocytes that are an important part of innate immunity because they are able to destroy tumor and virally infected cells without prior sensitization. Previous studies have shown that protein kinase D (PKD) in the NK cells has been activated in the presence of the environmental contaminant tributyltin (TBT) and that this may be part of the mechanism by which TBT blocks NK cell function. However, it is not known whether activation of PKD is part of the series of molecular signals that is activated in NK cells in the process of destroying target cells. This study was done to determine whether protein kinase D (PKD), a serine threonine kinase, within the NK cells can be activated in the presence of target cells (myelogenic leukemic derived cell line K562). In this study NK cells were exposed to K562 tumor cells for 10 min, 30 min and 1 h and cell lysates were prepared and analyzed by SDS‐PAGE followed by Western blot. The activation state of PKD was examined using antibody to phospho‐PKD. Protein kinase D was activated within the NK cell by the 10 min exposure to K562 tumor cells. There was approximately a 2 fold increase in activation of PKD in the presence of tumor cells. These results indicate that PKD is activated in the NK cell when it binds to tumors and thus, PKD activation is likely a part of the normal NK cell signaling pathway. Supported by grant S06 GM008092‐35