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Cited 16 time in webofscience Cited 17 time in scopus
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The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression

Authors
Park, Cho RongYou, Dong-JooPark, SumiMander, SunamJang, Da-EunYeom, Su-CheongOh, Seong-HyunAhn, CurieLee, Sang HeonSeong, Jae YoungHwang, Jong-Ik
Issue Date
14-Dec-2016
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v.6
Journal Title
SCIENTIFIC REPORTS
Volume
6
URI
https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7587
DOI
10.1038/srep39041
ISSN
2045-2322
Abstract
Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of beta-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses. In A549 lung cancer cells, which endogenously express CXCR1, the depletion of REEP5 and REEP6 significantly reduced growth and invasion by downregulating IL-8-stimulated ERK phosphorylation, actin polymerization and the expression of genes related to metastasis. Furthermore, an in vivo xenograft model showed that proliferation and metastasis of A549 cells lacking REEP5 and REEP6 were markedly decreased compared to the control group. Thus, REEP5 and REEP6 could be novel regulators of G-protein-coupled receptor signaling whose functional mechanisms differ from other accessory proteins.
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