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Phosphorylation of eukaryotic initiation factor 4E is dispensable for skeletal muscle hypertrophy.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2019 Dec 01; Vol. 317 (6), pp. C1247-C1255. Date of Electronic Publication: 2019 Oct 09. - Publication Year :
- 2019
-
Abstract
- The eukaryotic initiation factor 4E (eIF4E) is a major mRNA cap-binding protein that has a central role in translation initiation. Ser <superscript>209</superscript> is the single phosphorylation site within eIF4E and modulates its activity in response to MAPK pathway activation. It has been reported that phosphorylation of eIF4E at Ser <superscript>209</superscript> promotes translation of key mRNAs, such as cyclin D1, that regulate ribosome biogenesis. We hypothesized that phosphorylation at Ser <superscript>209</superscript> 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 synergist ablation to induce muscle hypertrophy of the plantaris muscle as the result of mechanical overload; in the KI mouse, Ser <superscript>209</superscript> of eIF4E was replaced with a nonphosphorylatable 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 synergist ablation. Similarly, the increases in cyclin D1 protein levels, ribosome biogenesis, and translational capacity did not differ between WT and KI groups. Based on these findings, we conclude that phosphorylation of eIF4E at Ser <superscript>209</superscript> is dispensable for skeletal muscle hypertrophy in response to mechanical overload.
- Subjects :
- Animals
Biomechanical Phenomena
Cyclin D1 genetics
Cyclin D1 metabolism
Eukaryotic Initiation Factor-4E metabolism
Female
Gene Expression Regulation
Gene Knock-In Techniques
Hypertrophy metabolism
Hypertrophy pathology
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal pathology
Nuclear Proteins genetics
Nuclear Proteins metabolism
Organelle Biogenesis
Phosphorylation
Proto-Oncogene Proteins c-myc genetics
Proto-Oncogene Proteins c-myc metabolism
RNA, Ribosomal genetics
RNA, Ribosomal metabolism
Ribosomes genetics
Ribosomes metabolism
Signal Transduction
Eukaryotic Initiation Factor-4E genetics
Hypertrophy genetics
Muscle, Skeletal metabolism
Protein Biosynthesis
Serine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1563
- Volume :
- 317
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 31596607
- Full Text :
- https://doi.org/10.1152/ajpcell.00380.2019