EFFECTS OF PROTEIN PHOSPHATASE INHIBITION BY OKADAIC ACID ON THE DIFFERENTIATION OF F9 EMBRYONAL CARCINOMA-CELLS

Okadaic acid, a protein phosphatase inhibitor, is a strong tumor promoter which apparently activates protein phosphorylation. To examine the role of protein phosphatases in stem cell growth and differentiation, embryonal carcinoma F9 cells were treated with okadaic acid. In the presence of this agent, the cells showed rapid morphological changes and arrest of proliferation at the M phase of the cell cycle, accompanied by a marked increase in the mRNA expression of various differentiation markers. Okadaic acid induced rapid increase in the mRNA levels of both c-jun and junB and stimulated AP-1 enhancer activity in F9 cells. These results indicate that the inhibition of phosphatase by okadaic acid induces apparent activation of protein phosphorylation and may cause the expression of differentiation marker genes in F9 cells via the activation of AP-1. (C) 1995 Academic Press, Inc.