Abstract
beta-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) and contribute to the desensitization of GPCRs by uncoupling the signal transduction process. Resensitization of GPCR responsiveness involves agonist-mediated receptor sequestration. Overexpression of beta-arrestins in human embryonic kidney cells rescued the sequestration of beta 2-adrenergic receptor (beta 2AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of beta-adrenergic receptor kinase 1. Wild-type beta 2AR sequestration was inhibited by the overexpression of two beta-arrestin mutants. These findings suggest that beta-arrestins play an integral role in GPCR internalization and thus serve a dual role in the regulation of GPCR function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic beta-Agonists / pharmacology*
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Antigens / genetics
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Antigens / physiology*
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Arrestins*
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Cell Line
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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DNA, Complementary
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Eye Proteins / genetics
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Eye Proteins / physiology*
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GTP-Binding Proteins / metabolism*
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Humans
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Isoproterenol / pharmacology
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Mutation
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Phosphorylation
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Point Mutation
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Receptors, Adrenergic, beta-2 / genetics
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Receptors, Adrenergic, beta-2 / metabolism*
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Transfection
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beta-Adrenergic Receptor Kinases
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beta-Arrestins
Substances
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Adrenergic beta-Agonists
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Antigens
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Arrestins
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DNA, Complementary
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Eye Proteins
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Receptors, Adrenergic, beta-2
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beta-Arrestins
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Cyclic AMP-Dependent Protein Kinases
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beta-Adrenergic Receptor Kinases
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GTP-Binding Proteins
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Isoproterenol