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

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

SUBMITTER: Das F

PROVIDER: S-EPMC2949510 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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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.

Das Falguni F Ghosh-Choudhury Nandini N Kasinath Balakuntalam S BS Choudhury Goutam Ghosh GG

FEBS letters 20100917 19

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 ac ...[more]

PMID: 20837011

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