Overexpression of protein kinase FA/GSK-3α (a proline-directed protein kinase) correlates with human hepatoma dedifferentiation/progression

✍ Scribed by Shiaw-Der Yang; Jau-Song Yu; Chuan-Ching Yang; Shan-Chih Lee; Tsong-Tze Lee; Mei-Hui Ni; Chu-Yun Kuan; Hsiang-Chin Chen

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 941 KB
• Volume: 61
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19960501)61:2<238::aid-jcb7>3.0.co;2-v

✦ Synopsis

Computer analysis of protein phosphorylation sites sequence revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glyCogen synthase kinase-3a (kinase F A / G S K -~~) (a member of PDPK family) has been optimized for human hepatoma and used to demonstrate for the first time significantly increased (P < 0.01) activity in poorly differentiated SK-Hep-I hepatoma (24.2 ? 2.8 unitsimg) and moderately differentiated Mahlavu hepatoma (1 4.5 * 2.2 units/mg) when compared to well differentiated Hep 38 hepatoma (8.0 +-2.4 units/mg). lmmunoblotting analysis revealed that increased activity of kinase FdGSK-3a is due to overexpression of the protein. Elevated kinase F A / G S K -~~ expression in human hepatoma biopsies relative to normal liver tissue was found to be even more profound. This kinase appeared to be -fivefold overexpressed in well differentiated hepatoma and -13-fold overexpressed in poorly differentiated hepatoma when compared to normal liver tissue. Taken together, the results provide initial evidence that overexpression of kinase F A / G S K -~~ is involved in human hepatoma dedifferentiation/progression. Since kinase F A / G S K -~~ is a PDPK, the results further support a potential role of this kinase in human liver tumorigenesis, especially in its dedifferentiationiprogres-SiOn. kt