Regulation of the phosphorylation of elongation factor 2 by MEK-dependent signalling in adult rat cardiomyocytes.
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.
Wang
Lijun
L
Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, UK.
Proud
Christopher G
CG
D000818:Animals; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology; D007700:Kinetics; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases; D020652:Peptide Elongation Factor 2; D010656:Phenylephrine; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; C546845:mTOR protein, rat; C512963:Rps6ka1 protein, rat