title: Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis.
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.
authors.affiliation: 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.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jiyoung Y
authors.initials: JY
authors.lastname: Cha
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Jo Woon
authors.initials: JW
authors.lastname: Seok
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Yoonjeong
authors.initials: Y
authors.lastname: Choi
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Yoon
authors.affiliation: 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.
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Choi
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Yu
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Song
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Kim
authors.affiliation: 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.|Department of Integrated OMICS for Biomedical Sciences, Graduate School, Yonsei University, Seoul 120-749, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Lee
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Daeun
authors.initials: D
authors.lastname: Kim
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Han
authors.affiliation: 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.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752, Korea.|Department of Integrated OMICS for Biomedical Sciences, Graduate School, Yonsei University, Seoul 120-749, Korea.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D021381:Protein Transport; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; C498511:Rasd1 protein, mouse; D018631:ras Proteins