Angiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes

Allen D. Everett, Tamara D. Stoops, Angus C. Nairn, David Brautigan

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Increased protein synthesis is the cardinal feature of cardiac hypertrophy. We have studied angiotensin II (ANG II)-dependent regulation of eukaryotic elongation factor-2 (eEF-2), an essential component of protein translation required for polypeptide elongation, in rat neonatal cardiac myocytes. eEF2 is fully active in its dephosphorylated state and is inhibited following phosphorylation by eEF2 kinase. ANG II treatment (10-10-10-7 M) for 30 min produced an AT1 receptor-specific and concentration- and time-dependent reduction in the phosphorylation of eEF-2. Protein phosphatase 2A (PP2A) inhibitors okadaic acid and fostriecin, but not the PP2B inhibitor FK506, attenuated ANG II-dependent dephosphorylation of eEF-2. ANG II activated mitogen-activated protein kinase, (MAPK) within 10 min of treatment, and blockade of MAPK activation with PD-98059 (1-20 nM) inhibited eEF-2 dephosphorylation. The effect of ANG II on eEF-2 dephosphorylation was also blocked by LY-29004 (1-20 nM), suggesting a role for phosphoinositide 3-kinase, but the mammalian target rapamycin inhibitor rapamycin (10-100 nM) had no effect. Together these results suggest that the ANG II-dependent increase in protein synthesis includes activation of eEF-2 via dephosphorylation by PP2A by a process that involves both PI3K and MAPK.

Original languageEnglish (US)
Pages (from-to)H161-H167
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number1 50-1
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Mitogen-activated protein kinase
  • Phosphoinositide 3-kinase
  • Protein phosphatase 2A
  • Protein translation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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