Abstract
Homologous or agonist-specific desensitization of beta-adrenergic receptors is thought to be mediated by a specific kinase, the beta-adrenergic receptor kinase (beta ARK). However, recent data suggest that a cofactor is required for this kinase to inhibit receptor function. The complementary DNA for such a cofactor was cloned and found to encode a 418-amino acid protein homologous to the retinal protein arrestin. The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors.
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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Amino Acid Sequence
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Animals
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Antigens / genetics*
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Antigens / isolation & purification
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Antigens / pharmacology
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Arrestin
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Blotting, Northern
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Chromatography, Ion Exchange
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Cloning, Molecular
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Cyclic AMP-Dependent Protein Kinases*
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DNA / genetics
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Eye Proteins / genetics*
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Eye Proteins / isolation & purification
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Eye Proteins / pharmacology
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Gene Expression Regulation
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Molecular Sequence Data
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Phosphodiesterase Inhibitors / pharmacology*
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Phosphorylation
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Protein Kinases / pharmacology*
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RNA, Messenger / analysis
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Receptors, Adrenergic, beta / drug effects*
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Receptors, Adrenergic, beta / physiology
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Transfection
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beta-Adrenergic Receptor Kinases
Substances
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Antigens
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Arrestin
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Eye Proteins
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Phosphodiesterase Inhibitors
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RNA, Messenger
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Receptors, Adrenergic, beta
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DNA
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Protein Kinases
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Cyclic AMP-Dependent Protein Kinases
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beta-Adrenergic Receptor Kinases