DYRK2 negatively regulates cardiomyocyte growth by mediating repressor function of GSK-3β on eIF2Bε

A prerequisite of hypertrophic response of the myocardium is an increase in protein synthesis. A central regulator of translation initiation is Eukaryotic initiation factor 2B (eIF2B). Here we assessed the hypothesis that regulation of protein synthesis via eIF2Bε is essential to cardiac hypertrophi...

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Bibliographic Details
Published in:PloS one 2013-09, Vol.8 (9), p.e70848
Main Authors: Weiss, Celine S, Ochs, Marco M, Hagenmueller, Marco, Streit, Marcus R, Malekar, Pratima, Riffel, Johannes H, Buss, Sebastian J, Weiss, Karl H, Sadoshima, Junichi, Katus, Hugo A, Hardt, Stefan E
Format: Article
Language:English
Subjects:
Animals
Aorta
Banding
Cardiomyocytes
Cells, Cultured
Dyrk Kinases
Echocardiography
Eukaryotic Initiation Factor-2B - genetics
Eukaryotic Initiation Factor-2B - metabolism
Glycogen Synthase Kinase 3 - genetics
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
Growth factors
Heart
Heart diseases
Heart failure
Hypertrophy, Left Ventricular - genetics
Hypertrophy, Left Ventricular - metabolism
Immunoprecipitation
In vivo methods and tests
Initiation factor eIF-2
Internal medicine
Isoproterenol
Kinases
Male
Medicine
Mice
Mice, Inbred C57BL
Mice, Transgenic
Myocardium
Myocytes
Myocytes, Cardiac - metabolism
Phosphorylation
Physiology
Priming
Protein biosynthesis
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Protein synthesis
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Proteins
Real-Time Polymerase Chain Reaction
Regulation
RNA, Small Interfering - genetics
Rodents
siRNA
Stimulation
Studies
Tibia
Transgenic mice
Translation initiation
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Summary:A prerequisite of hypertrophic response of the myocardium is an increase in protein synthesis. A central regulator of translation initiation is Eukaryotic initiation factor 2B (eIF2B). Here we assessed the hypothesis that regulation of protein synthesis via eIF2Bε is essential to cardiac hypertrophic response in vivo. Two transgenic mouse lines were generated with cardiac restricted overexpression of eIF2Bε or its mutant eIF2Bε-eIFS(535)A, which cannot be inactivated by phosphorylation through GSK-3β. (1) Under baseline conditions eIF2Bε transgenic mice showed no difference in cardiac phenotype compared to wild type, whereas in the mutant eIF2Bε-S(535)A an increase in LV/tibia length (7.5 ± 0.4 mg/mm vs. 6.2 ± 0.2 mg/mm, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0070848