Phosphorylation of eIF-4E and initiation of protein synthesis in P19 embryonal carcinoma cells.
Mitogenic stimulation of protein synthesis is accompanied by an increase in eIF-4E phosphorylation. The effect on protein synthesis by induction of differentiation is less well known. We treated P19 embryonal carcinoma cells with the differentiating agent retinoic acid and found that protein synthesis increased during the first hour of addition. However, the phosphorylation state, as well as the turnover of phosphate on eIF-4E, remained unchanged. Apparently, the change in protein synthesis after RA addition is regulated by another mechanism than eIF-4E phosphorylation. By using P19 cells overexpressing the EGF receptor, we show that the signal transduction pathway that leads to phosphorylation of eIF-4E is present in P19 cells; the EGF-induced change in phosphorylation of eIF-4E in these cells is likely to be regulated by a change in eIF-4E phosphatase activity. These results suggest that the onset of retinoic acid-induced differentiation is triggered by a signal transduction pathway which involves changes in protein synthesis, but not eIF-4E phosphorylation.
Kleijn
M
M
Department of Molecular Cell Biology, University of Utrecht, Netherlands.
Voorma
H O
HO
Thomas
A A
AA
D000595:Amino Acid Sequence; D002454:Cell Differentiation / Q000187:drug effects; D054278:Embryonal Carcinoma Stem Cells; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects; D039561:Eukaryotic Initiation Factor-4E; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D018243:Teratocarcinoma / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins; D010448:Peptide Initiation Factors; D010710:Phosphates; D014212:Tretinoin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors