Association of protein kinase FA/GSK-3α (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression

✍ Scribed by Dr. Shiaw-Der Yang; Jau-Song Yu; Tsong-Tze Lee; Mei-Hui Ni; Chuan-Ching Yang; Yat-Sen Ho; Tze-Zen Tsen

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 753 KB
• Volume: 59
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240590203

✦ Synopsis

Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of 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 FA/GSK-3a) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 * 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 5 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 2 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 ? 0.6 U/mg of protein). lmmunoblotting analysis further revealed that increased activity of kinase FA/GSK-3a in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3a may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3a may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3a may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.