INHIBITORS OF PHOSPHOPROTEIN PHOSPHATASE-1 AND PHOSPHATASE-2A CAUSE ACTIVATION OF A 53 KDA PROTEIN-KINASE ACCOMPANYING THE APOPTOTIC RESPONSE OF BREAST-CANCER CELLS

Treatment of MCF-7 breast cancer cells with 50 nM okadaic acid trigger s an apoptotic response which is accompanied by a 7-fold increase in t he activity of a protein kinase with a relative molecular mass of 53 k Da. The activity of the kinase was stimulated by cell treatment with i nhibitors of phosphoprotein phosphatase I and 2A, but not by stressing conditions. Okadaic acid-induced stimulation of the 53 kDa protein ki nase was not abolished by coincubation of cells with cycloheximide. We conclude that stimulation of the 53 kDa protein kinase by inhibitors of phosphoprotein phosphatases involves pre-existing molecular compone nts whose activity depends on the phosphorylation state of serine/thre onine residues. (C) 1997 Federation of European Biochemical Societies.