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

Hyo Jung Kim, Jiyoung Cha, Jo Woon Seok, Yoonjeong Choi, Bo Kyung Yoon, Hyeonjin Choi, Jung Hwan Yu, Su Jin Song, Ara Kim, Hyemin Lee, Daeun Kim, Ji Yoon Han, Jae Woo Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number28648
JournalScientific Reports
Volume6
DOIs
StatePublished - Jun 27 2016

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Adipogenesis
Somatomedins
Glucocorticoids
Adipocytes
Cell Membrane
Insulin
CCAAT-Enhancer-Binding Proteins
ras Proteins
Monomeric GTP-Binding Proteins
Epidermal Growth Factor
Obesity
Phosphorylation
Amino Acids

ASJC Scopus subject areas

  • General

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Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis. / Kim, Hyo Jung; Cha, Jiyoung; Seok, Jo Woon; Choi, Yoonjeong; Yoon, Bo Kyung; Choi, Hyeonjin; Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Lee, Hyemin; Kim, Daeun; Han, Ji Yoon; Kim, Jae Woo.

In: Scientific Reports, Vol. 6, 28648, 27.06.2016.

Research output: Contribution to journalArticle

Kim, HJ, Cha, J, Seok, JW, Choi, Y, Yoon, BK, Choi, H, Yu, JH, Song, SJ, Kim, A, Lee, H, Kim, D, Han, JY & Kim, JW 2016, 'Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis', Scientific Reports, vol. 6, 28648. https://doi.org/10.1038/srep28648
Kim, Hyo Jung ; Cha, Jiyoung ; Seok, Jo Woon ; Choi, Yoonjeong ; Yoon, Bo Kyung ; Choi, Hyeonjin ; Yu, Jung Hwan ; Song, Su Jin ; Kim, Ara ; Lee, Hyemin ; Kim, Daeun ; Han, Ji Yoon ; Kim, Jae Woo. / Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis. In: Scientific Reports. 2016 ; Vol. 6.
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