Enhanced expression and activation of Ca(2+)/calmodulin-dependent protein kinase IV in hepatocellular carcinoma.
BACKGROUND: Ca(2+)/calmodulin-dependent protein kinase IV (CaM-kinase IV) is a multifunctional protein kinase that is expressed abundantly in the central nervous system and, to a lesser degree, in nonneuronal tissues such as the liver. In the current study, the authors demonstrated the expression of CaM-kinase IV in hepatocytes from hepatocellular carcinoma ( HCC) in both humans and rats. METHODS: Immunoblotting and immunohistochemical analysis were performed to confirm the expression of CaM-kinase IV and CaM-kinase kinase in HCC occurring in both humans and rats. The kinase activity of CaM-kinase IV in the lysate of each of these liver supernatant fluids was measured using a specific substrate (peptide gamma) for this enzyme before and after phosphorylation by exogenously added CaM-kinase kinase. RESULTS: Marked positive staining of HCC hepatocytes was found and the subcellular staining pattern mainly was cytosolic. One immunoreactive band with a molecular weight of 64 kilodaltons, which was identical to an isoform of rat cerebellum CaM-kinase IV, was demonstrated by immunoblotting. Ca(2+)/calmodulin-dependent CaM-kinase IV activity was high in HCC and showed almost no difference in activity in specimens with and without CaM-kinase kinase phosphorylation. CONCLUSIONS: CaM-kinase IV was found to be expressed in HCC and might have been involved in the development of HCC. CaM-kinase IV that was expressed in cancerous hepatocytes was phosphorylated mainly by CaM-kinase kinase that also was expressed in tumor cells.[1]References
- Enhanced expression and activation of Ca(2+)/calmodulin-dependent protein kinase IV in hepatocellular carcinoma. Tamura, N., Tai, Y., Sugimoto, K., Kobayashi, R., Konishi, R., Nishioka, M., Masaki, T., Nagahata, S., Tokuda, M. Cancer (2000) [Pubmed]
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