Activity of glycogen synthase kinase-3beta is down-regulated during transient differentiation of human colon cancer HT-29 cells.
The increased phosphorylation and activity of protein kinase B (PKB/Akt) was found early upon butyrate treatment of HT-29 cells with a potent differentiating agent, sodium butyrate. It was accompanied by the increased phosphorylation of glycogen synthase kinase-3 (GSK-3) and the inhibition of the activity of GSK-3beta to catalyze phosphorylation of its substrate, translation initiation factor eIF2B. Phosphorylation of PKB and GSK-3 in HT-29 cells was reduced by wortmannin, the inhibitor of phosphatidylinositol-3' kinase (PI3'-kinase), which is upstream activator of PKB and GSK-3 in the intracellular signalling. Modulation of the activity and phosphorylation of these protein kinases during transient in vitro differentiation of HT-29 cells indicates that control of the PI3'-kinase/PKB-dependent signalling pathway may be implicated very early in the changes of malignant phenotype of HT-29 cells.
Tuhackova
Z
Z
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 166 37 Praha 6, Czech Republic.
Sloncova
E
E
Hlavacek
J
J
Sovova
V
V
Velek
J
J
D000730:Androstadienes / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002454:Cell Differentiation; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004794:Enzyme Repression; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D019073:HT29 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; C494918:AKT1 protein, human