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

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