TGFβ enforces activation of eukaryotic elongation factor-2 (eEF2) via inactivation of eEF2 kinase by p90 ribosomal S6 kinase (p90Rsk) to induce mesangial cell hypertrophy

Falguni Das, Nandini Ghosh-Choudhury, Balakuntalam S. Kasinath, Goutam Ghosh Choudhury

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

eEF2 phosphorylation is under tight control to maintain mRNA translation elongation. We report that TGFβ activates eEF2 by decreasing eEF2 phosphorylation and simultaneously increasing eEF2 kinase phosphorylation. Remarkably, inhibition of Erk1/2 blocked the TGFβ-induced dephosphorylation and phosphorylation of eEF2 and eEF2 kinase. TGFβ increased phosphorylation of p90Rsk in an Erk1/2-dependent manner. Inactive p90Rsk reversed TGFβ-inhibited phosphorylation of eEF2 and suppressed eEF2 kinase activity. Finally, inactive p90Rsk significantly attenuated TGFβ-induced protein synthesis and hypertrophy of mesangial cells. These results present the first evidence that TGFβ utilizes the two layered kinase module Erk/p90Rsk to activate eEF2 for increased protein synthesis during cellular hypertrophy.

Original languageEnglish (US)
Pages (from-to)4268-4272
Number of pages5
JournalFEBS Letters
Volume584
Issue number19
DOIs
StatePublished - Oct 1 2010

Keywords

  • Diabetic nephropathy
  • MRNA translation
  • Receptor serine/threonine kinase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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