Kinase-Inactive G-Protein-Coupled Receptor Kinases Are Able to Attenuate Follicle-Stimulating Hormone-Induced Signaling

详细信息    查看全文

• 作者：Reiter ; Eric ; Marion ; Sé ; bastien ; Robert ; Fabienne ; Troispoux ; Carine ; Boulay ; Franç ; ois ; et. al.
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2001
• 出版时间：March 23, 2001
• 年：2001
• 卷：282
• 期：1
• 页码：71-78
• 全文大小：185 K

文摘

Homologous desensitization of G-protein-coupled receptors (GPCR) is thought to occur in several steps: binding of G-protein-coupled receptor kinases (GRKs) to receptors, receptor phosphorylation, kinase dissociation, and finally binding of β-arrestin to phosphorylated receptors and functional uncoupling of the associated Gα protein. It has recently been reported that GRKs can inhibit Gαq-mediated signaling in the absence of phosphorylation of some GPCRs. Whether or not comparable phosphorylation-independent effects are also possible with Gαs-coupled receptors remains unclear. In the present study, using the tightly Gαs-coupled FSR receptor (FSH-R) as a model, we observed inhibition of the cAMP-dependent signaling pathway using kinase-inactive mutants of GRK2, 5, and 6. These negative effects occur upstream of adenylyl cyclase activation and are likely independent of GRK interaction with G protein α or β/γ subunits. Moreover, we demonstrated that, when overexpressed in Cos 7 cells, mutated GRK2 associates with the FSH activated FSH-R. We hypothesize that phosphorylation-independent dampening of the FSH-R-associated signaling could be attributable to physical association between GRKs and the receptor, subsequently inhibiting G protein activation.