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

Authors
 Hyo Jung Kim  ;  Jiyoung Y. 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 
Citation
 Scientific Reports, Vol.6 : 28648, 2016 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2016
MeSH
3T3-L1 Cells ; Adipocytes/metabolism* ; Adipogenesis* ; Animals ; Cell Membrane/genetics ; Cell Membrane/metabolism* ; Glucocorticoids/genetics ; Glucocorticoids/metabolism* ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism* ; MAP Kinase Signaling System* ; Male ; Mice ; Protein Transport ; ras Proteins/genetics ; ras Proteins/metabolism*
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.
DOI
10.1038/srep28648
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
김재우(Kim, Jae Woo) ORCID logo https://orcid.org/0000-0001-5456-9495
김효정(Kim, Hyo Jung) ORCID logo https://orcid.org/0000-0002-3514-1247
유정환(Yu, Jung Hwan)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147160
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