14-3-3 protein family members have a regulatory role in retinoic acid-mediated induction of cytokeratins in F9 cells

We have found that the expression of five 14-3-3 protein isoforms is induce d during the retinoic acid (RA)mediated differentiation of mouse embryonal carcinoma F9 cells. The induced expression of the 14-3-3 proteins is presum ed to have a role in enhancing the mitogen-activated protein kinase (MAPK) activity during RA-mediated F9 cell differentiation, because using genetica lly engineered budding yeast we showed that these isoforms enhanced the sig naling in the MAPK cascade mainly through the interaction with Raf-l. Then we assessed the role of increased MAPK activity in F9 cell differentiation by interfering with signaling in the MAPK cascade in F9 cells. The exogenou s expression of dominant-negative MEK1 efficiently abrogated RA-mediated in duction of the cytokeratins EndoA and EndoC in the F9 cells. These results suggest that the 14-3-3 proteins play a role in the efficient induction of the cytokeratins during F9 cell differentiation through their signal enhanc ing activity in the MAPK cascade, (C) 2000 Academic Press.