Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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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)
  • Received : 2009.09.29
  • Accepted : 2009.10.19
  • Published : 2009.12.31
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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

References

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