GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling.
Stimulation of cell-surface seven-transmembrane receptors (7TMRs) elicits biological responses to a wide range of extracellular signals, including many hormones. Classically, heterotrimeric GTP-binding proteins (G proteins) are recruited to the activated conformation of 7TMRs. Only two other families of protein have this remarkable characteristic: G-protein-coupled receptor kinases and beta-arrestins. These two protein families have long been known to have a central and coordinated role in the "desensitization" of G protein activation by 7TMRs. In addition, G-protein-coupled receptor kinases and beta-arrestins are involved in an increasing number of interactions with non-receptor proteins, broadening the variety of their cellular functions. These newly appreciated attributes of these two families of protein highlight their unique ability to coordinate the various aspects of 7TMR functions.
Reiter
Eric
E
Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Lefkowitz
Robert J
RJ
D000818:Animals; D019390:Arrestins / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology; D000071557:beta-Arrestins
D019390:Arrestins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D020794:Receptor Protein-Tyrosine Kinases; D020962:Heterotrimeric GTP-Binding Proteins