Atypical protein kinase C ι protects human leukemia cells against drug- induced apoptosis

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Abstract

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 β(II) is required for proliferation. In this report, we assess the role of the atypical PKC isoform PKC 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.

Original languageEnglish (US)
Pages (from-to)27521-27524
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number44
DOIs
StatePublished - Oct 31 1997
Externally publishedYes

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Protein Kinase C
Leukemia
Apoptosis
K562 Cells
Pharmaceutical Preparations
Okadaic Acid
PKC-3 protein
Cell Physiological Phenomena
Phosphoprotein Phosphatases
Physiology
Tetradecanoylphorbol Acetate
Paclitaxel
Isoenzymes
Cell Survival
Protein Isoforms
Plasmids
Complementary DNA
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Atypical protein kinase C ι protects human leukemia cells against drug- induced apoptosis. / Murray, Nicole R; Fields, Alan P.

In: Journal of Biological Chemistry, Vol. 272, No. 44, 31.10.1997, p. 27521-27524.

Research output: Contribution to journalArticle

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