Document Detail

Regulation of myostatin signaling by c-Jun N-terminal kinase in C2C12 cells.
MedLine Citation:
PMID:  17689926     Owner:  NLM     Status:  MEDLINE    
Myostatin, a member of the transforming growth factor beta (TGF-beta) superfamily, is a negative regulator of skeletal muscle growth. We found that myostatin could activate c-Jun N-terminal kinase (JNK) signaling pathway in both proliferating and differentiating C2C12 cells. Using small interfering RNA (siRNA) mediated activin receptor type IIB (ActRIIB) knockdown, the myostatin-induced JNK activation was significantly reduced, indicating that ActRIIB was required for JNK activation by myostatin. Transfection of C2C12 cells with TAK1-specific siRNA reduced myostatin-induced JNK activation. In addition, JNK could not be activated by myostatin when the expression of MKK4 was suppressed with MKK4-specific siRNA, suggesting that TAK1-MKK4 cascade was involved in myostatin-induced JNK activation. We also found that blocking JNK signaling pathway by pretreatment with JNK specific inhibitor SP600125, attenuated myostatin-induced upregulation of p21 and downregulation of the differentiation marker gene expression. Furthermore, it was also observed that the presence of SP600125 almost annulled the growth inhibitory role of myostatin. Our findings provide the first evidence to reveal the involvement of JNK signaling pathway in myostatin's function as a negative regulator of muscle growth.
Zhiqing Huang; Daiwen Chen; Keying Zhang; Bing Yu; Xiaoling Chen; Jianghong Meng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-08
Journal Detail:
Title:  Cellular signalling     Volume:  19     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-09-10     Completed Date:  2007-11-13     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  2286-95     Citation Subset:  IM    
Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan, PR China.
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MeSH Terms
Activin Receptors, Type II / metabolism
Cell Differentiation
Cell Proliferation
Cells, Cultured
Down-Regulation / genetics
Enzyme Activation
JNK Mitogen-Activated Protein Kinases / metabolism*
MAP Kinase Kinase Kinases / metabolism
Mitogen-Activated Protein Kinase Kinases / metabolism
Myoblasts / cytology,  enzymology*
RNA, Small Interfering / metabolism
Signal Transduction*
Transforming Growth Factor beta / metabolism*
Reg. No./Substance:
0/Mstn protein, mouse; 0/Myostatin; 0/RNA, Small Interfering; 0/Transforming Growth Factor beta; EC Mitogen-Activated Protein Kinases; EC Kinase Kinase Kinases; EC kinase kinase kinase 7; EC Receptors, Type II; EC receptor type II-B; EC Protein Kinase Kinases

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