RT Journal Article
SR Electronic
T1 Keeping G Proteins at Bay: A Complex Between G Protein-Coupled Receptor Kinase 2 and Gßγ
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1256
OP 1262
DO 10.1126/science.1082348
VO 300
IS 5623
A1 Lodowski, David T.
A1 Pitcher, Julie A.
A1 Capel, W. Darrell
A1 Lefkowitz, Robert J.
A1 Tesmer, John J. G.
YR 2003
UL http://science.sciencemag.org/content/300/5623/1256.abstract
AB The phosphorylation of heptahelical receptors by heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor kinases (GRKs) is a universal regulatory mechanism that leads to desensitization of G protein signaling and to the activation of alternative signaling pathways.We determined the crystallographic structure of bovine GRK2 in complex with G protein β1γ2 subunits.Our results show how the three domains of GRK2–the RGS (regulator of G protein signaling) homology, protein kinase, and pleckstrin homology domains–integrate their respective activities and recruit the enzyme to the cell membrane in an orientation that not only facilitates receptor phosphorylation, but also allows for the simultaneous inhibition of signaling by Gα and Gβγ subunits.