G-protein-coupled receptor kinases and the heart.

The family of G-protein-coupled receptors includes many well-studied members, such as the adrenergic and the muscarinic acetylcholine receptors. These receptors are regulated by multiple mechanisms that serve to adapt their expression and their function to a rapidly changing environment. One of the most intriguing and important regulatory mechanisms involves the phosphorylation of such receptors by a set of specific kinases, termed the G-protein-coupled receptor kinases (GRKs). This phosphorylation is followed by binding of specific arrestin proteins to the phosphorylated receptors, which uncouples the receptors from their G proteins and thus causes a loss of receptor function. Several isoforms of the GRKs and the arrestins are expressed in the heart. They may be involved in the loss of receptor function in response to drugs. Furthermore, increased expression of one of the GRKs, β-adrenergic receptor kinase-1, has been found in failing hearts, and its increased activity may contribute to the loss of β-adrenergic receptor function in heart failure.