G protein-coupled receptor kinases: Specific phosphorylation of 7TM receptors and beyond

G protein-coupled receptor kinases (GRK) have been classically considered as negative regulators of G protein-coupled receptors. However, cumulative evidence is putting forward novel roles for GRKs. These include a positive role in signal transmission based on differential receptor phosphorylation leading to the recruitment of distinct arrestin-orchestrated signalosomes as well as previously unforeseen regulatory functions in cell signaling routes unrelated to this family of seven-transmembrane receptors. These new functions and the targeting strategies available at present to address GRK biology are discussed in this review.

Section editors:Terence Kenakin – Glaxo Smith Kline, Systems Research 3-2104.2B, Research Triangle Park, NC 27709, USAAlan Wise – Edinburgh, UK