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http://dx.doi.org/10.1007/s10059-009-0167-z

Ligand-Independent Activation of the Androgen Receptor by Insulin-Like Growth Factor-I and the Role of the MAPK Pathway in Skeletal Muscle Cells  

Kim, Hye Jin (Department of Exercise Science, College of Health Sciences, Ewha Womans University)
Lee, Won Jun (Department of Exercise Science, College of Health Sciences, Ewha Womans University)
Publication Information
Molecules and Cells / v.28, no.6, 2009 , pp. 589-593 More about this Journal
Abstract
In this study, the roles of the p38 MAPK, ERK1/2 and JNK signaling pathway in IGF-I-induced AR induction and activation were examined. C2C12 cells were treated with IGF-I in the absence or presence of various inhibitors of p38 MAPK (SB203580), ERK1/2 (PD98059), and JNK (SP600125). Inhibition of the MAPK pathway with SB203580, PD98059, or SP600125 significantly decreased IGF-I-induced AR phosphorylation and total AR protein expression. IGF-I-induced nuclear fraction of total AR and phosphorylated AR were significantly inhibited by SB203580, PD98059, or SP600125. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by those inhibitors in dose-dependent manner. Confocal images showed that IGF-I-induced AR nuclear translocation from cytosol was significantly blocked by SB203580, PD98059, or SP600125, suggesting that the MAPK pathway regulates IGF-I-induced AR nuclear localization in skeletal muscle cells. The present results suggest that the MAPK pathways are required for the ligand-independent activation of AR by IGF-I in C2C12 skeletal muscle cells.
Keywords
androgen receptor; insulin-like growth factor-I; ligand-independent mechanism; mitogen-activated protein kinase; steroid receptor;
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