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• W2151775257 abstract "Two of the common mechanisms regulating G protein-coupled receptor (GPCR) signal transduction are phosphorylation and sequestration (internalization). Agonist-mediated receptor phosphorylation by the β-adrenergic receptor kinase (βARK) facilitates subsequent interaction with an arrestin protein, resulting in receptor desensitization. Studies of the β₂-adrenergic receptor (β₂AR) receptor in human embryonic kidney (HEK) 293 cells indicate that βARK and arrestin proteins (β-arrestins) also regulate sequestration. Consistent with this notion, we show in HEK 293 cells that reduction in or removal of the ability of the β₂AR to be phosphorylated by βARK or to interact normally with β-arrestin substantially reduces agonist-mediated sequestration. To evaluate βARK and β-arrestin regulation of β₂AR sequestration, we examined the relationship between βARK and/or β-arrestin expression and β₂AR sequestration in a variety of cultured cells, including HEK 293, COS 7, CHO, A431, and CHW. COS cells had both the lowest levels of endogenous β-arrestin expression and β₂AR sequestration, whereas HEK 293 had the highest. Overexpression of β-arrestin, but not βARK, in COS cells increased the extent of wild-type β₂AR sequestration to levels observed in HEK 293 cells. However, a βARK phosphorylation-impaired β₂AR mutant (Y326A) required the simultaneous overexpression of both βARK and β-arrestin for this to occur. Among all cell lines, sequestration correlated best with the product of βARK and β-arrestin expression. Moreover, an agonist-mediated translocation of wild-type β₂AR and endogenous β-arrestin 2 to endocytic vesicles prepared from CHO fibroblasts was observed. These data suggest not only that the complement of cellular βARK and arrestin proteins synergistically regulate β₂AR sequestration but also that β-arrestins directly regulate β₂AR trafficking as well as desensitization." @default.
• W2151775257 created "2016-06-24" @default.
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• W2151775257 date "1997-05-01" @default.
• W2151775257 modified "2023-09-28" @default.
• W2151775257 title "Synergistic Regulation of β₂-Adrenergic Receptor Sequestration: Intracellular Complement of β-Adrenergic Receptor Kinase and β-Arrestin Determine Kinetics of Internalization" @default.
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• W2151775257 doi "https://doi.org/10.1124/mol.51.5.800" @default.
• W2151775257 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9145918" @default.
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