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Am J Physiol Gastrointest Liver Physiol (February 12, 2004). doi:10.1152/ajpgi.00507.2003
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Submitted on December 3, 2003
Accepted on February 6, 2004

Pro-Apoptotic Function of Protein Kinase CK2{alpha}" is mediated by a JNK Signaling Cascade

Philip Hilgard1, Mark J. Czaja2, Guido Gerken1, and Richard J. Stockert2*

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

* To whom correspondence should be addressed. E-mail: stockert{at}aecom.yu.edu.

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 as compared to other tissues and is required for the normal trafficking of several hepatocellular membrane proteins. Initial studies of dengue virus (DEN) infection indicated that the CK2{alpha}''-deficient Trf1 mutant cell line was resistant to virus induced cell death compared to the parental HuH-7 hepatoma line. Expression of recombinant CK2{alpha}'' in Trf1 was capable of reverting this resistant phenotype. The 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 pro-apoptotic step in HuH-7 cells by CK2{alpha}'' is mediated by a JNK signaling cascade.




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