β-arrestin Promotes c-Jun N-terminal kinase mediated apoptosis via a GABABR·β-arrestin·JNK signaling module

Abstract

Evidence is growing that the GABAB receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies have shown that β-arrestin can serve as a scaffold to recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether β-arrestin recruits JNK to the GABAB receptor and facilitates its activation to affect the growth of cancer cells. Our results showed that β-arrestin expression is decreased in breast cancer cells in comparison with controls. β-arrestin could enhance interactions of the GABABR·β-arrestin·JNK signaling module in MCF-7 and T-47D cells. Further studies revealed that increased expression of β-arrestin enhances the phosphorylation of JNK and induces cancer cells apoptosis. Collectively, these results indicate that β-arrestin promotes JNK mediated apoptosis via a GABABR·β-arrestin·JNK signaling module.