Keeping the Signals Fresh

For cells to remain responsive to stimuli such as light or odor, activated G protein-coupled receptors (GPCRs) must be rapidly desensitized. G protein-coupled receptor kinases (GRKs) play a role in regulating G protein signaling by interacting both with GPCRs and with heterotrimeric G proteins. Lodowski et al. have determined the structure of GRK2 complexed to G protein βγ subunits (Gβγ). The three signaling domains of GRK2 act together to recruit GRK2 to the membrane and orient it to facilitate phosphorylation of GPCRs. This orientation would allow GRK2 to simultaneously bind the GPCR and Gβγ and Gα subunits and to provide a mechanism for efficient attenuation of heterotrimeric G protein signaling. D. T. Lodowski, J. A. Pitcher, W. D. Capel, R. J. Lefkowitz, J. J. G. Tesmer, Keeping G proteins at bay: A complex between G protein-coupled receptor kinase 2 and Gβγ. Science 300 , 1256-1262 (2003). [Abstract] [Full Text]