title: Activation of protein kinase C and protein kinase D in human natural killer cells: effects of tributyltin, dibutyltin, and tetrabromobisphenol A.
abstract: Up to now, the ability of target cells to activate protein kinase C (PKC) and protein kinase D (PKD) (which is often a downstream target of PKC) has not been examined in natural killer (NK) lymphocytes. Here we examined whether exposure of human NK cells to lysis sensitive tumor cells activated PKC and PKD. The results of these studies show for the first time that activation of PKC and PKD occurs in response to target cell binding to NK cells. Exposure of NK cells to K562 tumor cells for 10 and 30 min increased phosphorylation/activation of both PKC and PKD by roughly 2-fold. Butyltins (tributyltin (TBT), dibutyltin (DBT)) and brominated compounds (tetrabromobisphenol A (TBBPA)) are environmental contaminants that are found in human blood. Exposures of NK cells to TBT, DBT, or TBBPA decrease NK cell lytic function in part by activating the mitogen-activated protein kinases (MAPKs) that are part of the NK lytic pathway. We established that PKC and PKD are part of the lytic pathway upstream of MAPKs and thus we investigated whether DBT, TBT, and TBBPA exposures activated PKC and PKD. TBT-activated PKC by 2-3-folds at 10 min at concentrations ranging from 50 to 300 nM while DBT caused a 1.3-fold activation at 2.5 µM at 10 min. Both TBT and DBT caused an approximately 2-fold increase in phosphorylation/activation of PKC. Exposures to TBBPA caused no statistically significant changes in either PKC or PKD activation.
authors.affiliation: a Department of Biological Sciences and.
authors.forename: Krupa
authors.initials: K
authors.lastname: Rana
authors.affiliation: b Department of Chemistry , Tennessee State University , Nashville , TN , USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Whalen
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology; D009947:Organotin Compounds / Q000633:toxicity*; D010766:Phosphorylation; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D061251:Primary Cell Culture; D011493:Protein Kinase C / Q000378:metabolism*; D014220:Trialkyltin Compounds / Q000633:toxicity*
chemical_list: D009947:Organotin Compounds; D011075:Polybrominated Biphenyls; D014220:Trialkyltin Compounds; C056189:di-n-butyltin; C011559:tributyltin; C089212:protein kinase D; D011493:Protein Kinase C; C020806:tetrabromobisphenol A
keywords: Brominated flame retardants; NK cells; PKC; PKD; butyltins