*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 7961702


    		J Biol Chem. 1994 Nov 11;269(45):27791-4.
     
			Palmitoylation of G protein-coupled receptor
			kinase, GRK6. Lipid modification diversity
			in the GRK family.

			Stoffel RH(1), Randall RR, Premont RT, Lefkowitz
			RJ, Inglese J.

			Author Information
			(1) Howard Hughes Medical Institute,
			Duke University Medical Center, Durham,
			North Carolina 27710.

			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.

			PMID: 7961702 [Indexed for MEDLINE]

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