Overexpression of cellular activity and protein level of protein kinase FA/GSK-3 alpha correlates with human thyroid tumor cell dedifferentiation.
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-3 alpha (kinase FA/GSK-3 alpha) (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 FA/GSK-3 alpha in thyroid tumor cells is due to overexpression of the protein synthesis of the enzyme. Taken together, the results provide initial evidence that overexpression of protein level and cellular activity of kinase FA/GSK-3 alpha is involved in human thyroid tumor cell dedifferentiation, supporting an association of PDPK with neoplastic transformation and tumorigenesis. Since kinase FA/GSK-3 alpha may function as a possible regulator of transcription factors/protooncogenes, kinase FA/GSK-3 alpha may therefore play an important role in thyroid cell carcinogenesis, especially in its differentiation.
Lee
T T
TT
Institute of Biomedical and Life Sciences, National Tsing Hua University, Hsinchu, Republic of China.
Ho
Y S
YS
Yu
J S
JS
Yang
S D
SD
D000236:Adenoma / Q000201:enzymology / Q000473:pathology; D000595:Amino Acid Sequence; D000906:Antibodies; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000096:biosynthesis*; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012016:Reference Values; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology*
D000906:Antibodies; D008869:Microtubule-Associated Proteins; D010455:Peptides; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3