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

Reiter, Eric; Marion, Sébastien; Robert, Florian; Troispoux, Carine; Boulay, François; Guillou, Florian; Crépieux, Pascale

doi:10.1006/bbrc.2001.4534

Cited by 30 publications

(20 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that the granulosa cellular viability was unaffected by a combination of GnIH and FSH treatments. GnIH and FSH are likely to activate antagonistic signaling pathways mediated by G ai2 and G as respectively (Reiter et al 2001, Ikemoto & Park 2005. Such antagonism may, at least in part, explain the lack of inhibitory effect of GnIH on granulosa cellular viability in the presence of FSH.…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-inhibitory hormone (GnIH) receptor gene is expressed in the chicken ovary: potential role of GnIH in follicular maturation

et al. 2008

View full text Add to dashboard Cite

Gonadotropin-inhibitory hormone (GnIH), an RFamide peptide, has been found to inhibit pituitary LH secretion in avian and mammalian species. The gene encoding a putative receptor for GnIH (GnIHR) was recently identified in the chicken and Japanese quail brain and pituitary gland. GnIHR appears to be a seven-transmembrane protein belonging to a family of G-protein-coupled receptors. In the present study, we have characterized the expression of GnIHR mRNA in the chicken ovary and demonstrate that GnIHR may exert an inhibitory effect on ovarian follicular development. By RT-PCR, we detected GnIHR mRNA in the chicken testis and in the ovary, specifically both thecal and granulosa cell layers. Real-time quantitative PCR analysis revealed greater GnIHR mRNA quantity in theca cells of prehierarchial follicles compared with that of preovulatory follicles. GnIHR mRNA quantity was significantly decreased in sexually mature chicken ovaries versus ovaries of sexually immature chickens. Estradiol (E 2 ) and/or progesterone (P 4 ) treatment of sexually immature chickens significantly decreased ovarian GnIHR mRNA abundance. Treatment of prehierarchial follicular granulosa cells in vitro with chicken GnIH peptide significantly decreased basal but not FSH-stimulated cellular viability. Collectively, our results indicate that the ovarian GnIHR is likely to be involved in ovarian follicular development. A decrease in ovarian GnIHR mRNA abundance due to sexual maturation or by E 2 and/or P 4 treatment would implicate an inhibitory role for GnIHR in ovarian follicular development. Furthermore, GnIH may affect follicular maturation by decreasing the viability of prehierarchial follicular granulosa cells through binding to GnIHR.

show abstract

Section: Discussionmentioning

confidence: 99%

Gonadotropin-inhibitory hormone (GnIH) receptor gene is expressed in the chicken ovary: potential role of GnIH in follicular maturation

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Using this type of approaches, it has been demonstrated that different GRKs and b-arrestins are involved in regulating the internalization and signaling of the FSH-R (Lazari et al 1999, Troispoux et al 1999, Reiter et al 2001, Kishi et al 2002, Marion et al 2002, Krishnamurthy et al 2003a, 2003b. However, when expressed above the physiological level, the stoichiometry of these factors within signaling complexes is altered and this might ultimately modify GRK and/or b-arrestin specificity.…”

Section: Discussionmentioning

confidence: 99%

“…Sertoli cells were prepared from testes of 12-day-old rats (Wistar, Janvier, France), according to a previously described method (Crepieux et al 2001). The study was performed according to the European legislative, administrative and statutory measures concerning the protection of animals used for experimental or other scientific purposes (86/609/EEC).…”

Section: Cell Culturementioning

confidence: 99%

“…When overexpressed, different GRKs phosphorylate the FSH-R in an agonist-dependent manner and desensitize cAMP production (Lazari et al 1999, Troispoux et al 1999, Reiter et al 2001, Kishi et al 2002, Marion et al 2002, Krishnamurthy et al 2003a, 2003b. The interaction of the phosphorylated FSH-R with b-arrestins is essential for its functional uncoupling (Lazari et al 1999, Troispoux et al 1999.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

G protein-coupled receptor kinase 2 and β-arrestins are recruited to FSH receptor in stimulated rat primary Sertoli cells

Marion

Kara

Crépieux

et al. 2006

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

FSH-receptor (FSH-R) signaling is regulated by agonistinduced desensitization and internalization. It has been shown, in a variety of overexpression systems, that G protein-coupled receptor kinases (GRKs) phosphorylate the activated FSH-R, promote b-arrestin recruitment and ultimately lead to internalization. The accuracy of this mechanism has not yet been demonstrated in cells expressing these different molecules at physiological levels. Using sucrose gradient fractionation, we show that FSH induces the recruitment of the endogenous GRK 2 and b-arrestin 1/2 from the cytoplasm to the plasma membrane of rat primary Sertoli cells. As assessed by ligand binding, the FSH-R was found expressed in the fractions where GRK 2 and b-arrestins were recruited upon FSH treatment. In addition, the endogenous b-arrestin 1 was found dephosphorylated in an agonist-dependent manner. Finally, a significant FSH-binding activity was co-immunoprecipitated with the endogenous b-arrestins from agonist-stimulated but not from untreated Sertoli cell extracts. This FSH-R interaction with b-arrestins was sustained for up to 30 min. In conclusion, our data strongly suggest that the GRK/b-arrestin machinery plays a physiologically relevant role in the regulation of the FSH signaling.

show abstract

“…Third, we have now identified mGluR1a and mGluR1b point mutants that do not bind GRK2 and are not sensitive to GRK2 overexpression. Finally, the GRK phosphorylation-independent regulation of GPCR activity may not be unique to mGluR1 because other G␣ s -, G␣ i -, and G␣ q/11 -coupled GPCRs have been reported to associate with GRKs and desensitize in the absence of GRK kinase activity (17,18,35,36). Taken together, these observations indicate that formation of receptor⅐GRK complexes may lead to the phosphorylation-and arrestin-independent inhibition of GPCR signaling.…”

Section: Figmentioning

confidence: 96%

Phosphorylation-independent Regulation of Metabotropic Glutamate Receptor 1 Signaling Requires G Protein-coupled Receptor Kinase 2 Binding to the Second Intracellular Loop

Dhami

Babwah

Sterne‐Marr

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Metabotropic glutamate receptors (mGluRs) are members of a unique class of G protein-coupled receptors (class III) that include the calcium-sensing and ␥-aminobutyric acid type B receptors. The activity of mGluRs is regulated by second messenger-dependent protein kinases and G protein-coupled receptor kinases (GRKs). The attenuation of both mGluR1a and mGluR1b signaling by GRK2 is phosphorylation-and ␤-arrestin-independent and requires the concomitant association of GRK2 with both the receptor and G␣ q/11 . G protein interactions are mediated, in part, by the mGluR1 intracellular second loop, but the domains required for GRK2 binding are unknown. In the present study, we showed that GRK2 binds to the second intracellular loop of mGluR1a and mGluR1b and also to the mGluR1a carboxyl-terminal tail. Alanine scanning mutagenesis revealed a discrete domain within loop 2 that contributes to GRK2 binding, and the mutation of either lysine 691 or 692 to an alanine within this domain resulted in a loss of GRK2 binding to both mGluR1a and mGluR1b. Mutation of either Lys 691 or Lys 692 prevented GRK2-mediated attenuation of mGluR1b signaling, whereas the mutation of only Lys 692 prevented GRK2-mediated inhibition of mGluR1a signaling. Thus, the mGluR1a carboxyl-terminal tail may also be involved in regulating the signaling of the mGluR1a splice variant. Taken together, our findings indicated that kinase binding to an mGluR1 domain involved in G protein-coupling is essential for the phosphorylation-independent attenuation of signaling by GRK2.Metabotropic glutamate receptors (mGluRs) 1 comprise a family of eight G protein-coupled receptors (GPCRs) that are activated by the excitatory amino acid glutamate and play an important role in regulating neuronal development and synaptic plasticity (1-3). Group I mGluRs (mGluR1 and mGluR5) are coupled via the heterotrimeric G protein G␣ q/11 to the activation of phospholipase C, resulting in the formation of both inositol 1,4,5-triphosphate and diacylglycerol, as well as increases in intracellular Ca 2ϩ concentrations. The alternative gene splicing of mGluR1 generates five carboxyl-terminal domain mGluR1 splice variants (1a, 1b, 1c, 1d, and 1e) (1-4). The G protein-coupling domain for these slice variants is conserved, and it is mediated by amino acid residues localized within the second and third intracellular loops and the membrane proximal region of the mGluR1 carboxyl-terminal tail (4).Similar to most GPCRs, mGluR activity is regulated by serine/threonine protein kinases (5-9). In general, the desensitization of GPCRs involves either phosphorylation by second messenger-dependent protein kinase or phosphorylation by G protein-coupled receptor kinases (GRKs) to promote the binding of arrestin proteins (10, 11). GRK2, GRK4, and GRK5 have each been demonstrated to contribute to the desensitization and internalization of mGluR1 in both heterologous cell cultures and Purkinje cells (5)(6)(7)(12)(13)(14)(15). Although GRK2 and GRK4 promote the ␤-arrestin-dependent internalization of mGlu...

show abstract

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

Cited by 30 publications

References 38 publications

Gonadotropin-inhibitory hormone (GnIH) receptor gene is expressed in the chicken ovary: potential role of GnIH in follicular maturation

Gonadotropin-inhibitory hormone (GnIH) receptor gene is expressed in the chicken ovary: potential role of GnIH in follicular maturation

G protein-coupled receptor kinase 2 and β-arrestins are recruited to FSH receptor in stimulated rat primary Sertoli cells

Phosphorylation-independent Regulation of Metabotropic Glutamate Receptor 1 Signaling Requires G Protein-coupled Receptor Kinase 2 Binding to the Second Intracellular Loop

Contact Info

Product

Resources

About