Function of the alpha 1 beta 2 gamma 2S gamma-aminobutyric acid type A receptor is modulated by protein kinase C via multiple phosphorylation sites.

Details

Serval ID
serval:BIB_69BA48CA18FF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Function of the alpha 1 beta 2 gamma 2S gamma-aminobutyric acid type A receptor is modulated by protein kinase C via multiple phosphorylation sites.
Journal
Journal of Biological Chemistry
Author(s)
Kellenberger S., Malherbe P., Sigel E.
ISSN
0021-9258[print], 0021-9258[linking]
Publication state
Published
Issued date
1992
Volume
267
Number
36
Pages
25660-25663
Language
english
Abstract
Activation of protein kinase C (PKC) results in down-modulation of the gamma-aminobutyric acid type A (GABAA) receptor. In this study, the recombinant subunit combination alpha 1 beta 2 gamma 2S was expressed in Xenopus oocytes. The resulting channel was shown to be modulated by 2 microM oleoylacetylglycerol or, stereo-specifically, by low concentrations (10 nM) of the phorbol ester 4 beta-phorbol 12-myristate 13-acetate. By site-specific mutagenesis, we altered the serine or threonine residues of consensus phosphorylation sites for PKC in the large, intracellular domain of alpha 1, beta 2, and gamma 2S. Mutant subunits were co-expressed with wild type subunits to yield alpha 1 beta 2 gamma 2S combinations. All of the tested 14 mutations did not affect the level of expression of GABA current. Two of these mutations, Ser-410 in beta 2 and Ser-327 in gamma 2S, resulted in a significant reduction of the effect of the activator of PKC, 4 beta-phorbol 12-myristate 13-acetate, on the GABA current amplitude. Thus, we have identified two single serine residues, Ser-410 in the subunit beta 2 and Ser-327 in gamma 2S, as phosphorylation sites of a PKC endogenous to Xenopus oocytes. Co-expression of the mutant subunits suggests that phosphorylation of both sites is required for a full, PKC-mediated down-regulation of GABA currents.
Keywords
Animals, Base Sequence, Brain/metabolism, Diglycerides/pharmacology, Down-Regulation, Kinetics, Macromolecular Substances, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides, Oocytes/drug effects, Oocytes/metabolism, Phosphorylation, Protein Kinase C/metabolism, Rats, Receptors, GABA-A/drug effects, Receptors, GABA-A/genetics, Recombinant Proteins/drug effects, Recombinant Proteins/metabolism, Tetradecanoylphorbol Acetate/pharmacology, Xenopus
Pubmed
Web of science
Create date
24/01/2008 12:45
Last modification date
20/08/2019 14:24
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