Am J Physiol Cell Physiol. 2019 Oct 9. doi: 10.1152/ajpcell.00380.2019. [Epub ahead of print]

Phosphorylation of eIF4E is dispensable for skeletal muscle hypertrophy.

Author information

College of Health Sciences, Department of Rehabilitation Sciences, the Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, United States.
College of Medicine, Department of Physiology, the Center for Muscle Biology, University of Kentucky, Lexington, KY 40536, United States.


The eukaryotic initiation factor 4E (eIF4E) is a major mRNA cap-binding protein that has a central role in translation initiation. Serine 209 (Ser209) is the single phosphorylation site within eIF4E and modulates its activity in response to MAPK pathway activation. Previous studies have reported that phosphorylation of eIF4E Ser209 promotes translation of key mRNAs such as cyclin D1 that regulate ribosome biogenesis. We hypothesized that phosphorylation of Ser209 is required for skeletal muscle growth in response to a hypertrophic stimulus by promoting ribosome biogenesis. To test this hypothesis, wild-type (WT) and eIF4E Knocked-In (KI) mice were subjected to synergistic ablation to induce muscle hypertrophy of the plantaris muscle as the result of mechanical overload; the KI mouse has Ser209 of eIF4E replaced with a non-phosphorylatable alanine. Contrary to our hypothesis, we observed no difference in the magnitude of hypertrophy between WT and KI groups in response to 14 days of mechanical overload induced by synergistic ablation. Similarly, the increases in cyclin D1 protein levels, ribosome biogenesis and translational capacity were not different between WT and KI groups. Based on these findings, we conclude that phosphorylation of Ser209 of eIF4E is dispensable for muscle skeletal muscle hypertrophy in response to mechanical overload.


protein synthesis; ribosome biogenesis; skeletal muscle growth; translation

PMID: 31596607 
DOI: 10.1152/ajpcell.00380.2019
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