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http://dx.doi.org/10.7314/APJCP.2014.15.2.1041

β-arrestin Promotes c-Jun N-terminal Kinase Mediated Apoptosis via a GABABR·β-arrestin·JNK Signaling Module  

Wu, Jin-Xia (The First Clinical Medical College, Nanjing Medical University)
Shan, Feng-Xiao (Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College)
Zheng, Jun-Nian (The First Clinical Medical College, Nanjing Medical University)
Pei, Dong-Sheng (The First Clinical Medical College, Nanjing Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.2, 2014 , pp. 1041-1046 More about this Journal
Abstract
Evidence is growing that the $GABA_B$ receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies have shown that ${\beta}$-arrestin can serve as a scaffold to recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether ${\beta}$-arrestin recruits JNK to the $GABA_B$ receptor and facilitates its activation to affect the growth of cancer cells. Our results showed that ${\beta}$-arrestin expression is decreased in breast cancer cells in comparison with controls. ${\beta}$-arrestin could enhance interactions of the $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module in MCF-7 and T-47D cells. Further studies revealed that increased expression of ${\beta}$-arrestin enhances the phosphorylation of JNK and induces cancer cells apoptosis. Collectively, these results indicate that ${\beta}$-arrestin promotes JNK mediated apoptosis via a $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module.
Keywords
${\beta}$-arrestin; $GABA_B$ receptor; JNK; apoptosis;
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