Overexpression of cellular activity and protein level of protein kinase FA/GSK-3α correlates with human thyroid tumor cell dedifferentiation

Abstract 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 F_A/glycogen synthase kinase-3α (kinase F_A/GSK-3α) (a member of the PDPK family) has been optimized for human thyroid tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in thyroid carcinoma (24.2 ± 2.8 units/mg of protein) (n = 7), thyroid adenoma (14.5 ± 2.2 units/mg of protein) (n = 6), and thyroid hyperplasia (8.0 ± 2.4 units/mg of protein) (n = 5) when compared to five normal controls (4.1 ± 1.8 units/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase F_A/GSK-3α in thyroid tumor cells is due to overexpression of protein level and cellular activity of kinase F_A/GSK-3α is involved in human thyroid tumor cell dedifferentiation, supporting an association of PDPK with neoplastic transformation and tumorigenesis. Since kinase F_A/GSK-3α may function as a possible regulator of transcription factors/protooncogenes, kinase F_A/GSK-3α may therefore play an important role in thyroid cell carcinogenesis, especially in its differentiation.