Regulation of the phosphorylation of elongation factor 2 by MEK-dependent signalling in adult rat cardiomyocytes

FEBS Lett. 2002 Nov 6;531(2):285-9. doi: 10.1016/s0014-5793(02)03536-6.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Endothelin-1 / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Heart Ventricles / cytology
  • Kinetics
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / physiology*
  • Myocardium / enzymology*
  • Myocardium / metabolism
  • Peptide Elongation Factor 2 / metabolism*
  • Phenylephrine / pharmacology
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Protein Kinases / physiology
  • Rats
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • TOR Serine-Threonine Kinases

Substances

  • Endothelin-1
  • Enzyme Inhibitors
  • Peptide Elongation Factor 2
  • Protein Kinase Inhibitors
  • Phenylephrine
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • mTOR protein, rat
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Rps6ka1 protein, rat
  • Mitogen-Activated Protein Kinase Kinases