Abstract

Homologous or agonist-specific desensitization of βべーた-adrenergic receptors is thought to be mediated by a specific kinase, the βべーた-adrenergic receptor kinase (βべーた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 βべーた-arrestin, was expressed and partially purified. It inhibited the signaling function of βべーたARK-phosphorylated βべーた-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that βべーた-arrestin in concert with βべーたARK effects homologous desensitization of βべーた-adrenergic receptors.