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

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 F_A/glycogen synthase kinase-3α (kinase F_A/GSK-3α) (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 ± 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 ± 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). Immunoblotting analysis further revealed that increased activity of kinase F_A/GSK-3α 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 of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase F_A/GSK-3α 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 F_A/GSK-3α may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase F_A/GSK-3α may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression. © 1995 Wiley-Liss, Inc.