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Palmitoylation of G protein-coupled receptor kinase, GRK6. Lipid modification diversity in the GRK family
Ist Teil von
The Journal of biological chemistry, 1994-11, Vol.269 (45), p.27791-27794
Ort / Verlag
United States: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1994
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
GRK6, a 66-kDa serine/threonine protein kinase, is a recently identified member of the G protein-coupled receptor kinase (GRK)
family. GRKs are involved in the phosphorylation of seven-transmembrane receptors, a process mediating desensitization of
signal transduction. An important feature of these enzymes is their membrane-associated nature, which for some members is
stimulus-dependent. The structural basis for this membrane association previously has been shown in different members of the
GRK family to include isoprenylation, G protein beta gamma-binding domains, and basic regions to provide electrostatic interactions
with phospholipids. We provide evidence that another mechanism includes fatty acid acylation. GRK6, but not other GRKs tested,
incorporated tritium after incubation with [3H]palmitate in Sf9 and in COS-7 cells overexpressing the kinase. The incorporated
radioactivity was released from the protein by neutral hydroxylamine, indicating the presence of a thioester bond, and was
confirmed as palmitic acid by high performance liquid chromatography analysis. Site-directed mutagenesis defined the region
of palmitate attachment as a cluster of 3 cysteines (Cys561, Cys562, and Cys565) in the carboxyl-terminal domain of the kinase,
consistent with the location of the membrane targeting domains of GRKs 1, 2, 3, and 5. Palmitoylation of GRK6 appears essential
for membrane association, since palmitoylated kinase was found only in the membrane fraction. This lipid modification provides
a structural basis for potential regulation of the subcellular distribution of GRK6 through acylation/deacylation cycles.