Ethanol alters the subcellular localization of delta- and epsilon protein kinase C in NG108-15 cells.
Protein kinase C (PKC) has been shown to regulate the ethanol sensitivity of membrane-bound receptors and transporters, but little is known about the molecular mechanisms underlying this regulation. PKC is a family of isozymes that translocate to new intracellular sites on activation. Here we present immunochemical data showing that ethanol causes translocation of delta- and epsilon-PKC to new intracellular sites. Ethanol causes translocation of delta-PKC from the Golgi to the perinucleus; this translocation is similar to that induced by activation of PKC with phorbol esters. In contrast, epsilon-PKC translocation caused by ethanol is different from that induced by phorbol esters; ethanol causes translocation of epsilon-PKC from the perinucleus to the cytoplasm, whereas phorbol ester activation causes translocation of epsilon-PKC to the nucleus. Because the substrate specificity of these kinases is determined by their site of localization, ethanol-induced translocation of delta- and epsilon-PKC to new intracellular sites may explain some of the pleiotropic effects of ethanol on cellular functions.
Gordon
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AS
Ernest Gallo Clinic and Research Center and Department of Neurology, University of California, San Francisco, California 94110, USA.
Yao
L
L
Wu
Z L
ZL
Coe
I R
IR
Diamond
I
I
D001692:Biological Transport; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D013347:Subcellular Fractions / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D000431:Ethanol; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate