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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
Author(s) -
Das Falguni,
Ghosh-Choudhury Nandini,
Kasinath Balakuntalam S.,
Choudhury Goutam Ghosh
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.09.010
Subject(s) - phosphorylation , kinase , elongation factor , microbiology and biotechnology , dephosphorylation , biology , protein kinase a , biochemistry , chemistry , ribosome , phosphatase , rna , gene
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.