title: β-arrestin promotes c-Jun N-terminal kinase mediated apoptosis via a GABA(B)R·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.
authors.affiliation: The First Clinical Medical College, Nanjing Medical University, Nanjing, China E-mail : jnzheng@xzmc.edu.cn; dspei@xzmc.edu.cn.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Wu
authors.forename: Feng-Xiao
authors.initials: FX
authors.lastname: Shan
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Pei
mesh_terms: D017209:Apoptosis; D019390:Arrestins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D018080:Receptors, GABA-B / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D014408:Biomarkers, Tumor; D018080:Receptors, GABA-B; D000071557:beta-Arrestins; D048031:JNK Mitogen-Activated Protein Kinases