PHOSPHORYLATION OF ELF-4E AND INITIATION OF PROTEIN-SYNTHESIS IN P19 EMBRYONAL CARCINOMA-CELLS

Mitogenic stimulation of protein synthesis is accompanied by an increa se in elF-4E phosphorylation. The effect on protein synthesis by induc tion of differentiation is less well known. We treated P19 embryonal c arcinoma cells with the differentiating agent retinoic acid and found that protein synthesis increased during the first hour of addition. Ho wever, the phosphorylation state, as well as the turnover of phosphate on elF-4E, remained unchanged. Apparently, the change in protein synt hesis after RA addition is regulated by another mechanism than elF-4E phosphorylation. By using P19 cells overexpressing the EGF receptor, w e show that the signal transduction pathway that leads to phosphorylat ion of elF-4E is present in P19 cells; the EGF-induced change in phosp horylation of elF-4E in these cells is likely to be regulated by a cha nge in elF-4E phosphatase activity. These results suggest that the ons et of retinoic acid-induced differentiation is triggered by a signal t ransduction pathway which involves changes in protein synthesis, but n ot elF-4E phosphorylation. (C) 1995 Wiley-Liss, Inc.