ATYPICAL PROTEIN-KINASE-C-IOTA PROTECTS HUMAN LEUKEMIA-CELLS AGAINST DRUG-INDUCED APOPTOSIS

Protein kinase C (PHC) isozymes play distinct roles in cellular functi on. In human K562 leukemia cells, PKC alpha is important for cellular differentiation and PKC beta(II) is required for proliferation. In thi s report, we assess the role of the atypical PKC isoform PKC iota in H 562 leukemia cell physiology. K562 cells were stably transfected with expression plasmids containing the cDNA for human PKC iota in sense or antisense orientation to increase or decrease cellular PKC iota level s, respectively. Overexpression or inhibition of expression of PKC iot a had no significant effect on the proliferative capacity of K562 cell s nor their sensitivity to phorbol myristate acetate-induced cytostasi s and megakaryocytic differentiation, suggesting that PKC iota does no t play a critical role in these processes, Rather, PKC iota serves to protect K562 cells against drug-induced apoptosis, K562 cells, which a re resistant to most apoptotic agents, undergo apoptosis when treated with the protein phosphatase inhibitor okadaic acid (OA). Overexpressi on of PKC iota leads to increased resistance to OA induced apoptosis w hereas inhibition of PKC iota expression sensitizes cells to OA-induce d apoptosis, Overexpression of the related atypical PKC zeta has no pr otective effect, demonstrating that the effect is isotype-specific, PK C iota also protects K562 cells against taxol-induced apoptosis, indic ating that it plays a general protective role against apoptotic stimul i. These data support a role for PKC iota in leukemia cell survival.