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 scaffoldto recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether β-arrestinrecruits JNK to the GABAB receptor and facilitates its activation to affect the growth of cancer cells. Our resultsshowed that β-arrestin expression is decreased in breast cancer cells in comparison with controls. β-arrestincould enhance interactions of the GABABR·β-arrestin·JNK signaling module in MCF-7 and T-47D cells. Furtherstudies revealed that increased expression of β-arrestin enhances the phosphorylation of JNK and inducescancer cells apoptosis. Collectively, these resul