RSK2 mediates muscle cell differentiation through regulation of NFAT3

Yong Yeon Cho, Ke Yao, Ann M. Bode, H. Robert Bergen, Benjamin J. Madden, Sang Muk Oh, Svetlana Ermakova, Seok Kang Bong, Seok Choi Hong, Jung Hyun Shim, Zigang Dong

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

RSK2, an ERK downstream kinase, is a novel mediator of skeletal muscle cell differentiation through its regulation of NFAT3 activity. We found that the N-terminal (amino acids (aa) 1-68) and C-terminal (aa 416-674) kinase domains of RSK2 directly interacted with nuclear localization signal 1, the Ser/Pro repeat, and the polyproline domains (aa 261-365) of NFAT3. Upon A23187 stimulation, RSK2 induced nuclear localization of NFAT3. RSK2 phosphorylated NFAT3 in vitro (Km = 3.559 μM), and activation of NFAT3 by RSK2 enhanced the promoter activity of NFAT3 downstream target genes in vivo. Furthermore, nuclear accumulation of NFAT3 was attenuated markedly in RSK2 -/- cells compared with wild-type RSK2+/+ cells. Notably, RSK2 and NFAT3 induced a significant differentiation of C2C12 myoblasts to multinucleated myotubes. Multinucleated myotube differentiation was inhibited by small interfering RNA against RSK2, ERK1/2, or NFAT3. These results demonstrate that RSK2 is an important kinase for NFAT3 in mediating myotube differentiation.

Original languageEnglish (US)
Pages (from-to)8380-8392
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number11
DOIs
StatePublished - Mar 16 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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