Mol. Cells 2009; 28(6): 589-593
Published online November 19, 2009
https://doi.org/10.1007/s10059-009-0167-z
© The Korean Society for Molecular and Cellular Biology
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 pho-sphorylation 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 α-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
Mol. Cells 2009; 28(6): 589-593
Published online December 31, 2009 https://doi.org/10.1007/s10059-009-0167-z
Copyright © The Korean Society for Molecular and Cellular Biology.
Hye Jin Kim, and Won Jun Lee
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 pho-sphorylation 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 α-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
Won Jun Lee
Mol. Cells 2009; 28(5): 495-499 https://doi.org/10.1007/s10059-009-0142-8Hye Jin Kim, and Won Jun Lee
Mol. Cells 2009; 28(3): 189-194 https://doi.org/10.1007/s10059-009-0118-8Taewan Kim, Kwanyoung Jeong, Eunji Kim, Kwanghyun Yoon, Jinmi Choi, Jae Hyeon Park, Jae-Hwan Kim, Hyung Sik Kim, Hong-Duk Youn, and Eun-Jung Cho
Mol. Cells 2022; 45(4): 202-215 https://doi.org/10.14348/molcells.2021.0206