Ankrd2/ARPP is a novel Akt2 specific substrate and regulates myogenic differentiation upon cellular exposure to H 2O 2

Vittoria Cenni, Alberto Bavelloni, Francesca Beretti, Francesca Tagliavini, Lucia Manzoli, Giovanna Lattanzi, Nadir M. Maraldi, Lucio Cocco, Sandra Marmiroli

Research output: Contribution to journalArticle

Abstract

Activation of Akt-mediated signaling pathways is crucial for survival, differentiation, and regeneration of muscle cells. A proteomic-based search for novel substrates of Akt was therefore undertaken in C 2C 12 murine muscle cells exploiting protein characterization databases in combination with an anti-phospho-Akt substrate antibody. A Scansite database search predicted Ankrd2 (Ankyrin repeat domain protein 2, also known as ARPP) as a novel substrate of Akt. In vitro and in vivo studies confirmed that Akt phosphorylates Ankrd2 at Ser-99. Moreover, by kinase assay with recombinant Akt1 and Akt2, as well as by single-isoform silencing, we demonstrated that Ankrd2 is a specific substrate of Akt2. Ankrd2 is typically found in skeletal muscle cells, where it mediates the transcriptional response to stress conditions. In an attempt to investigate the physiological implications of Ankrd2 phosphorylation by Akt2, we found that oxidative stress induced by H 2O 2 triggers this phosphorylation. Moreover, the forced expression of a phosphorylation-defective mutant form of Ankrd2 in C 2C 12 myoblasts promoted a faster differentiation program, implicating Akt-dependent phosphorylation at Ser-99 in the negative regulation of myogenesis in response to stress conditions.

Original languageEnglish
Pages (from-to)2946-2956
Number of pages11
JournalMolecular Biology of the Cell
Volume22
Issue number16
DOIs
Publication statusPublished - Aug 15 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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