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

@article{citeulike:4908514, abstract = {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.}, author = {Reiter, Eric and Marion, S\'{e}bastien and Robert, Fabienne and Troispoux, Carine and Boulay, Fran\c{c}ois and Guillou, Florian and Crepieux, Pascale}, citeulike-article-id = {4908514}, citeulike-linkout-0 = {http://dx.doi.org/10.1006/bbrc.2001.4534}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0006291X01945346}, day = {23}, doi = {10.1006/bbrc.2001.4534}, issn = {0006291X}, journal = {Biochemical and Biophysical Research Communications}, keywords = {fsh, gpcr, kinase, signaling}, month = {March}, number = {1}, pages = {71--78}, posted-at = {2009-06-19 15:54:02}, priority = {0}, title = {Kinase-Inactive G-Protein-Coupled Receptor Kinases Are Able to Attenuate Follicle-Stimulating Hormone-Induced Signaling}, url = {http://dx.doi.org/10.1006/bbrc.2001.4534}, volume = {282}, year = {2001} }

TY - JOUR ID - citeulike:4908514 L3 - citeulike-article-id:4908514 N2 - 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. IS - 1 JF - Biochemical and Biophysical Research Communications SN - 0006291X EP - 78 TI - Kinase-Inactive G-Protein-Coupled Receptor Kinases Are Able to Attenuate Follicle-Stimulating Hormone-Induced Signaling VL - 282 SP - 71 KW - fsh KW - gpcr KW - kinase KW - signaling AU - Reiter, Eric AU - Marion, Sébastien AU - Robert, Fabienne AU - Troispoux, Carine AU - Boulay, François AU - Guillou, Florian AU - Crepieux, Pascale PY - 2001/03/23/ UR - http://dx.doi.org/10.1006/bbrc.2001.4534 ER -