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Am J Physiol Gastrointest Liver Physiol 287: G192-G201, 2004. First published February 12, 2004; doi:10.1152/ajpgi.00507.2003
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LIVER AND BILIARY TRACT

Proapoptotic function of protein kinase CK2{alpha}" is mediated by a JNK signaling cascade

Philip Hilgard,1 Mark J. Czaja,2 Guido Gerken,1 and Richard J. Stockert2

1Department for Gastroenterology and Hepatology, University-Hospital Essen, 45133 Essen, Germany; and 2Marion Bessin Liver Research Center and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, 10461

Submitted 3 December 2003 ; accepted in final form 6 February 2004

Protein kinase CK2 (formerly casein kinase II) is a tetrameric enzyme constitutively expressed in all eurakyotic tissues that plays a significant role in the regulation of cell proliferation, malignant transformation, and apoptosis. The catalytic {alpha}-subunit of the enzyme is known to exist in three isoforms CK2{alpha}, CK2{alpha}' and CK2{alpha}". CK2{alpha}" is highly expressed in liver compared with other tissues and is required for the normal trafficking of several hepatocellular membrane proteins. Initial studies of dengue virus infection indicated that the CK2{alpha}"-deficient membrane trafficking mutant cell line (Trf1) was resistant to virus-induced cell death compared with the parental human hepatoma (HuH)-7 hepatoma line. Expression of recombinant CK2{alpha}" in Trf1 was capable of reverting this resistant phenotype. This study was extended to TNF-{alpha} in addition to other stimuli of cell death in an attempt to uncover common death pathways that might be modulated by CK2{alpha}". Evaluation of different pathways involved in death signaling suggest that the regulation of a critical proapoptotic step in HuH-7 cells by CK2{alpha}" is mediated by a JNK signaling cascade.

dengue virus; tumor necrosis factor; activator protein-1; casein kinase


Address for reprint requests and other correspondence: R. Stockert, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Ave., Ullmann Bldg. Rm. 611, Bronx, NY, 10461 (E-mail: stockert{at}aecom.yu.edu).




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