Phosphoprotein phosphatase 2A dephosphorylates eIF-4E and does not alter binding to the mRNA cap.
The phosphorylation and dephosphorylation of the 25 kDa mRNA cap binding protein eukaryotic initiation factor-4E (eIF-4E) is regulated during different physiologic and pathophysiologic states that include cell growth and the late phase of adenovirus infection. We have found that okadaic acid is much more effective in increasing the phosphorylated fraction of eIF-4E than phorbol 12-myristate 13-acetate in Hep G2 cells. Phosphoprotein phosphatase 2A dephosphorylated eIF-4E isolated from both phorbol 12-myristate 13-acetate- or okadaic acid-treated cells, whereas alkaline and acid phosphatase were relatively ineffective. The ability of purified [35S]eIF-4E isolated from okadaic acid-treated cells to bind mRNA caps was compared to phosphoprotein phosphatase 2A-treated [35S]eIF-4E and found to be no different. This suggests that alternative explanations for the previously observed effects of eIF-4E phosphorylation on protein synthesis must be considered. In addition, our results indicate that the in vivo phosphorylation of eIF-4E is not catalyzed solely by protein kinase C.
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Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
Hagedorn
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D004988:Ethers, Cyclic / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D006801:Humans; D008099:Liver / Q000201:enzymology; D008954:Models, Biological; D019319:Okadaic Acid; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2; D012315:RNA Caps / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004988:Ethers, Cyclic; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012315:RNA Caps; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D013755:Tetradecanoylphorbol Acetate