Postnatal Development of β-Adrenergic Receptor Kinase Activity in Different Tissues of the Rat

Abstract

Recent studies have suggested a key role for the phosphorylation of plasma membrane receptors in the modulation of the sensitivity of cells to extracellular signals. Receptor phosphorylation has been proposed to regulate either receptor function or intracellular distribution, and has been shown to be implicated in the molecular mechanisms of desensitization (1,2). Desensitization is a widespread phenomenon characterized by the fact that the intensity of a response wanes over time despite the presence of a stimulus of constant intensity. Several recent investigations, utilizing the β-adrenergic receptor (βAR) system as a model, have demonstrated that desensitization of adenylate cyclase (AC) coupled receptors is associated with receptor phosphorylation by different protein kinases. Whereas the phosphorylation of βAR by cAMP-dependent protein kinase and protein kinase C contribute to different forms of “heterologous” regulation (1), Lefkowitz and col. have recently identified a novel protein kinase, termed β-adrenergic receptor kinase (βARK) that has been implicated in the molecular mechanisms of “homologous” or agonist-specific desensitization. βARK is a ubiquitously distributed cytosolic enzyme that phosphorylates only the agonist-occupied form of the βAR, up to 9 mol of phosphate per mol of receptor (3). βARK may also be capable of agonist-dependent phosphorylation of a variety of receptors coupled to either stimulation or inhibition of AC, thus emerging as an enzyme of general regulatory significance (4,5). However, very little is known about the physiological role of βARK.