Atypical Protein Kinase C ι Protects Human Leukemia Cells against Drug-induced Apoptosis

• Published in: The Journal of biological chemistry 1997-10, Vol.272 (44), p.27521-27524
• Main Authors: Murray, Nicole R., Fields, Alan P.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Division - drug effects; Drug Resistance, Neoplasm; Humans; Isoenzymes - metabolism; Leukemia, Erythroblastic, Acute - enzymology; Leukemia, Erythroblastic, Acute - pathology; Protein Kinase C - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.44.27521

Protein kinase C (PKC) isozymes play distinct roles in cellular function. In human K562 leukemia cells, PKC α is important for cellular differentiation and PKC βIIis required for proliferation. In this report, we assess the role of the atypical PKC isoform PKC ι in K562 leukemia cell physiology. K562 cells were stably transfected with expression plasmids containing the cDNA for human PKC ι in sense or antisense orientation to increase or decrease cellular PKC ι levels, respectively. Overexpression or inhibition of expression of PKC ι had no significant effect on the proliferative capacity of K562 cells nor their sensitivity to phorbol myristate acetate-induced cytostasis and megakaryocytic differentiation, suggesting that PKC ι does not play a critical role in these processes. Rather, PKC ι serves to protect K562 cells against drug-induced apoptosis. K562 cells, which are resistant to most apoptotic agents, undergo apoptosis when treated with the protein phosphatase inhibitor okadaic acid (OA). Overexpression of PKC ι leads to increased resistance to OA-induced apoptosis whereas inhibition of PKC ι expression sensitizes cells to OA-induced apoptosis. Overexpression of the related atypical PKC ζ has no protective effect, demonstrating that the effect is isotype-specific. PKC ι also protects K562 cells against taxol-induced apoptosis, indicating that it plays a general protective role against apoptotic stimuli. These data support a role for PKC ι in leukemia cell survival.