Abstract
The Gq-coupled agonists phenylephrine and endothelin-1 each activate protein synthesis in cardiomyocytes as part of the programme that leads to cardiac hypertrophy. Here we show that they each induce the dephosphorylation of elongation factor (eEF) 2, a protein that in its dephosphorylated state mediates the translocation step of elongation. The ability of both agonists to induce dephosphorylation of eEF2 requires signalling via the mTOR and MEK/Erk signalling pathways, but is independent of phosphoinositide 3-kinase. Expression of an activated form of MEK leads to dephosphorylation of eEF2, in an mTOR independent manner, indicating that signalling via MEK/Erk suffices to cause dephosphorylation of eEF2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Endothelin-1 / pharmacology
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Enzyme Inhibitors / pharmacology
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Heart Ventricles / cytology
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Kinetics
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MAP Kinase Signaling System*
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Kinases / physiology*
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Myocardium / enzymology*
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Myocardium / metabolism
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Peptide Elongation Factor 2 / metabolism*
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Phenylephrine / pharmacology
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Phosphatidylinositol 3-Kinases / physiology
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Phosphorylation
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Protein Kinase Inhibitors
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Protein Kinases / physiology
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Rats
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism
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TOR Serine-Threonine Kinases
Substances
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Endothelin-1
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Enzyme Inhibitors
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Peptide Elongation Factor 2
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Protein Kinase Inhibitors
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Phenylephrine
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Protein Kinases
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mTOR protein, rat
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Ribosomal Protein S6 Kinases, 90-kDa
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Rps6ka1 protein, rat
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TOR Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase Kinases