G protein-coupled receptors mediate signal from a wide array of molecules ranging from neurotransmitters, hormones, chemokiness, autacoid substances to light and odorants. Binding of agonists to its receptor leads to several molecular events ending in the second messengers production and in a variety of cellular function. For G protein-coupled receptors a patterns of rapid desensitization have been characterized, named homologous desensitization, mainly determined by G protein-coupled receptor kinases and arrestins. G protein-coupled receptor kinases are a family of serine/threonline protein kinases that appears to quench the response of a large number of GPCR by phosphorylating their C-terminal region or third intracellular loop. The multigene family of GRKs consists so far of six members named GRK 1 to 6 according to the order of their discovery. Arrestin is considered a GRK cofactor capable to bind to the activated phosphorylated receptor then induces maximal homologous desensitization. A recent report suggests that the binding of arrestin to the receptor may be a step towards initiation of receptor sequestration. So far many homologs have been coloned and the arrestin gene family consists of four recognized families: (1) Rhodopsin arrestin or S-antigen (arr), (2) ß-arrestin 1 (ßarr1), (3) ß-arrestin 2 (ßarr2) and (4) cone arrestin (Carr). Studies on regulation of GRKs and arrestins in vitro and in vivo confirm that the functional state of this machinery may have important consequences for cellular responsiveness and may represent new targets for therapeutic strategies.
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