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| OLFACTORY DESENSITIZATION REQUIRES MEMBRANE TARGETING OF RECEPTOR KINASE MEDIATED BY BETA-GAMMA-SUBUNITS OF HETEROTRIMERIC G-PROTEINS |
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| Author(s): BOEKHOFF I, INGLESE J, SCHLEICHER S, KOCH WJ, LEFKOWITZ RJ, BREER H |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 269 Issue: 1 Pages: 37-40 Published: JAN 7 1994 |
| Times Cited: 74 References: 32 |
| Abstract: Olfaction is mediated by G protein-coupled receptors. In isolated rat olfactory cilia, odorants such as citralva stimulate a burst of cAMP, which peaks in 50 ms and returns almost to base-line level within 150 ms in the continuing presence of odorant. This desensitization is mediated by the cAMP dependent protein kinase and a specialized G protein-coupled receptor kinase originally termed betaARK2BAR (GRK3). In vitro experiments suggest that the prenylated betagamma-subunits of heterotrimeric G proteins target the cytosolic betaARK1 (GRK2) enzyme to its membrane bound receptor substrate by binding to sites in its carboxyl terminus. Here we demonstrate that odorants stimulate translocation of GRK3 from cytosol to membranes in isolated rat olfactory cilia. We introduced a glutathione S-transferase-GRK3ct fusion protein, containing the carboxyl-terminal 222 amino acid residues of GRK3, which includes the betagamma binding site, or a 28-amino acid peptide derived therefrom, into permeabilized cilia preparations. These reagents block odorant-mediated enzyme translocation and desensitization while markedly attenuating odorant-stimulated phosphorylation of olfactory proteins. These findings suggest that betaggamma-subunits may physiologically regulate a G protein-coupled receptor kinase and that enzyme translocation may be a general and required feature of the activity of some members of this enzyme family. |
| Document Type: Note |
| Language: English |
Addresses:
1. DUKE UNIV, MED CTR, HOWARD HUGHES MED INST, DEPT MED, BOX 3821, DURHAM, NC 27710 USA
2. UNIV HOHENHEIM, DEPT ZOOPHYSIOL, D-70593 STUTTGART, GERMANY
3. DUKE UNIV, MED CTR, HOWARD HUGHES MED INST, DEPT BIOCHEM, DURHAM, NC 27710 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: MR219 |
| ISSN: 0021-9258 |
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