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RSK2 Mediates Muscle Cell Differentiation through Regulation of NFAT3

Year: 2007
Type: article
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 microM), 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.
DOI: 10.1074/jbc.m611322200
Authors: Yong-Yeon Cho, Ke Yao, Ann M. Bode, H. Robert Bergen, Benjamin J. Madden, Sang-Muk Oh, Svetlana Ermakova, Bong Seok Kang, Hong Seok Choi, Jung-Hyun Shim, Zigang Dong
Language: English
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: Study on Ultraviolet-induced Signal Transduction, INHIBITION OF CARCINOGENESIS BY TEA AND TEA CONSTITUENTS, Anticarcinogenic Mechanisms of Tea Constituents, G577899588, Anticarcinogenic Mechanisms of Tea Constituents, Chemoprevention of Skin Cancer Program Project
OpenAlex ID: W2097041188
FWCI: 1.85
Cites: 54
Cited by: 91
Related to: 10