Involvement of G protein-coupled receptor kinases and arrestins in desensitization to follicle-stimulating hormone action
| Autor: | Luisa Iacovelli, Antonio De Blasi, Carine Troispoux, Florian Guillou, Dmitri Firsov, Jean-Marc Elalouf, Eric Reiter, Yves Combarnous |
|---|---|
| Přispěvatelé: | Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
endocrine system
medicine.medical_specialty Arrestins Recombinant Fusion Proteins medicine.medical_treatment [SDV]Life Sciences [q-bio] Gene Expression Endogeny [INFO] Computer Science [cs] Transfection DNA Antisense Cell Line 03 medical and health sciences Endocrinology GTP-Binding Proteins Genes Reporter Internal medicine FSH Cyclic AMP medicine Arrestin Animals [INFO]Computer Science [cs] Luciferases Receptor Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology Desensitization (medicine) 0303 health sciences G protein-coupled receptor kinase biology Kinase Beta adrenergic receptor kinase 030302 biochemistry & molecular biology Receptor Protein-Tyrosine Kinases General Medicine Rats [SDV] Life Sciences [q-bio] Gene Expression Regulation biology.protein Receptors FSH RAT Follicle Stimulating Hormone hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Endocrinology-Baltimore Molecular Endocrinology-Baltimore-, Endocrine Society, 1999, 13, pp.1599-1614 |
| ISSN: | 0888-8809 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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