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- W2000150364 abstract "The G protein-coupled receptor (GPCR) G2A (for G2 accumulation) was identified as a stress-inducible antiproliferative cell cycle regulator. Targeted G2A gene deletion in mice resulted in systemic lupus erythematosus-like and atherosclerotic lesion phenotypes. These findings suggested that G2A may be a therapeutic target for cancers and autoimmune and cardiovascular diseases. The G2A receptor is cytotoxic upon ectopic expression, and its cognate ligand has not been identified, making it difficult to generate a cell line for screening using a conventional approach. The function of human G2A remains obscure. Here we show that by using an inducible T-REx™ (Invitrogen, Carlsbad, CA) expression system an inducible G2A functional cell-based β-lactamase reporter assay could be developed using the constitutive activity of the receptor. Furthermore, G2A expression levels can be controlled under this inducible system to avoid the expression artifacts of conventional approaches using constitutive expression vectors. This stable cell line expressing the human G2A receptor was screened against a chemical library containing 740,000 compounds, and small molecules showing selective agonistic activity on G2A were identified. We believe the strategy employed here for G2A should be applicable to other “intractable” GPCRs where target gene expression results in cytotoxic and/or high constitutive activities." @default.
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- W2000150364 date "2009-04-01" @default.
- W2000150364 modified "2023-10-10" @default.
- W2000150364 title "Agonists of the Orphan Human G2A Receptor Identified from Inducible G2A Expression and β-Lactamase Reporter Screen" @default.
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- W2000150364 doi "https://doi.org/10.1089/adt.2008.179" @default.
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