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Sci Rep. 2016 Jun 27;6:28648. doi: 10.1038/srep28648.

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis.

Kim HJ1, Cha JY2, Seok JW1,3, Choi Y1,3, Yoon BK1,3, Choi H1, Yu JH1,3, Song SJ1,3, Kim A1,3, Lee H1,4, Kim D1,3, Han JY1,3, Kim JW1,3,4.

Author information

1
Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
2
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
4
Department of Integrated OMICS for Biomedical Sciences, Graduate School, Yonsei University, Seoul 120-749, Korea.

Abstract

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223-276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis.

PMID:
27345868
PMCID:
PMC4921850
DOI:
10.1038/srep28648
[Indexed for MEDLINE]
Free PMC Article

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