Activity of glycogen synthase kinase-3 beta is down-regulated during transient differentiation of human colon cancer HT-29 cells

The increased phosphorylation and activity of protein kinase B (PKB/Akt) wa s found early upon butyrate treatment of HT-29 cells with a potent differen tiating agent, sodium butyrate. It was accompanied by the increased phospho rylation of glycogen synthase kinase-3 (GSK-3) and the inhibition of the ac tivity of GSK-3 beta to catalyze phosphorylation of its substrate, translat ion initiation factor eIF2B. Phosphorylation of PKB and GSK-3 in HT-29 cell s was reduced by wortmannin, the inhibitor of phosphatidylinositol-3' kinas e (PI3'-kinase), which is upstream activator of PKB and GSK-3 in the intrac ellular signalling. Modulation of the activity and phosphorylation of these protein kinases during transient in vitro differentiation of HT-29 cells i ndicates that control of the PI3'-kinase/PKB-dependent signalling pathway m ay be implicated very early. in the changes of malignant phenotype of HT-29 cells.