Article: article d'un périodique ou d'un magazine.
Involvement of G protein-coupled receptor kinases and arrestins in desensitization to follicle-stimulating hormone action.
Date de publication
FSH rapidly desensitizes the FSH-receptor (FSH-R) upon binding. Very little information is available concerning the regulatory proteins involved in this process. In the present study, we investigated whether G protein-coupled receptor kinases (GRKs) and arrestins have a role in FSH-R desensitization, using a mouse Ltk 7/12 cell line stably overexpressing the rat FSH-R as a model. We found that these cells, which express GRK2, GRK3, GRK5, and GRK6 as well as beta-arrestins 1 and 2 as detected by RT-PCR and by Western blotting, were rapidly desensitized in the presence of FSH. Overexpression of GRKs and/or beta-arrestins in Ltk 7/12 cells allowed us to demonstrate 1) that GRK2, -3, -5, -6a, and -6b inhibit the FSH-R-mediated signaling (from 71% to 96% of maximal inhibition depending on the kinase, P < 0.001); 2) that beta-arrestins 1 or 2 also decrease the FSH action when overexpressed (80% of maximal inhibition, P < 0.01) whereas dominant negative beta-arrestin 2 [319-418] potentiates it 8-fold (P < 0.001); 3) that beta-arrestins and GRKs (except GRK6a) exert additive inhibition on FSH-induced response; and 4) that FSH-R desensitization depends upon the endogenous expression of GRKs, since there is potentiation of the FSH response (2- to 3-fold, P < 0.05) with antisenses cDNAs for GRK2, -5, and -6, but not GRK3. Our results show that the desensitization of the FSH-induced response involves the GRK/arrestin system.
Animals, Arrestins/genetics, Arrestins/physiology, Cell Line, Cyclic AMP/metabolism, DNA, Antisense/pharmacology, Follicle Stimulating Hormone/pharmacology, GTP-Binding Proteins/metabolism, Gene Expression, Gene Expression Regulation/drug effects, Genes, Reporter/genetics, Luciferases/drug effects, Luciferases/genetics, Rats, Receptor Protein-Tyrosine Kinases/genetics, Receptor Protein-Tyrosine Kinases/physiology, Receptors, FSH/drug effects, Receptors, FSH/genetics, Recombinant Fusion Proteins/drug effects, Recombinant Fusion Proteins/genetics, Transfection
Web of science
Création de la notice
Dernière modification de la notice