The range of signals acting through G protein-coupled receptors include numerous neurotransmitters, chemoattractants, hormones, cytokines, and sensory stimuli such as photons or odorants. A general property of such signal transduction systems is that in the face of continuing stimulation signaling becomes attenuated by processes referred to as desensitization, tachyphylaxis, adaptation, tolerance, or quenching. While a number of quite distinct mechanisms have been found to participate in such regulation, control of receptor function appears to be particularly important. Among the several mechanisms that can regulate receptors, rapid modulation of their function by an emerging family of receptor serine/threonine kinases has been increasingly appreciated (Hausdorff et al., 1990; Palczewski and Benovic, 1991). Rapid phosphorylation of many G protein-coupled receptors accompanies stimulus-driven desensitization. Two types of kinases are known to mediate these modifications: second messenger kinases and novel G proteincoupled receptor kinases. In the former group, both the cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) have been shown to phosphorylate and regulate the adenylate cyclase-coupled 132-adrenergic receptor as well as other receptors (Hausdorff et al., 1990). These second messenger kinase pathways provide potential mechanisms for classical feedback regulatory loops or for so-called cross-talk between different second messenger systems.

G protein-coupled receptor kinases, a more recently discovered family, have the unique feature of phosphorylating G protein-coupled receptors only when they are in their active or stimulated conformations (Palczewski and Benovic, 1991). The best-studied members of this family are~-adrenergic receptor kinase 1 (~ ARK1)(Benovic et al., 1989) and rhodopsin kinase (Lorenz et al., 1991), both named originally for their preferred receptor substrates. Current understanding, as schematically represented in Figure 1, is that phosphorylation of the active receptor is followed by binding of a second protein, arrestin in the visual system and 13-arrestin in the 13-adrenergic receptor system. Binding of the arrestin molecule presumably interdicts signal transduction between the receptor and G protein by steric mechanisms.