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Ovarian Kaleidoscope Database (OKdb)

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G protein-coupled receptor kinase 6 OKDB#: 2558
 Symbols: GRK6 Species: human
 Synonyms: GPRK6,GRK6  Locus: 5q35 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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DNA Microarrays
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link to BioGPS
General Comment Found in an ovulation array.

NCBI Summary: This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
General function Intracellular signaling cascade
Comment
Cellular localization Cytoskeleton
Comment
Ovarian function Steroid metabolism
Comment
Expression regulated by FSH, Steroids
Comment
Ovarian localization Oocyte
Comment GRK-6 mediates FSH action synergistically enhanced by estrogen and the oocyte in rat granulosa cells. Miyoshi T et al. Estrogen is known to play a pivotal role in granulosa cell responses to follicle-stimulating hormone (FSH) that is critical for the establishment of dominant follicles and subsequent ovulation in mammals. Thus, elucidating the cellular and molecular mechanisms that regulate FSH activity is important to understand female fertility. We previously discovered that the oocyte is required for estrogen to exert its positive effects on FSH activity in rat granulosa cells. This finding supports the new concept that estrogen action in granulosa cells is mediated by the oocyte. In the current study, we explored the underlying mechanism. In the presence of oocytes, estrogens enhanced FSH-induced increases in aromatase, steroidogenic acute regulatory protein and FSH receptor mRNA expression as well as cAMP production. However, as forskolin did not mimic FSH activity this indicated that coexistence of estrogen/oocytes increases FSH activity at a site upstream of adenylate cyclase in granulosa cells. We therefore sought a possible involvement of the autoregulatory molecules for FSH receptor, G protein-coupled receptor kinases (GRKs) and ?arrestins in enhancing FSH activity in response to the estrogen/oocyte co-treatment in granulosa cells. Among the seven known GRK and two ?arrestin molecules, we found that estrogens with oocytes suppressed FSH-induced GRK-6 mRNA expression. Consistent with this finding, transfecting granulosa cells with small interfering RNA of GRK-6 significantly increased FSH induction of aromatase mRNA, suggesting that endogenous GRK-6 plays an inhibitory role in FSH-induced aromatase mRNA expression. Consequently, these findings strongly suggest that GRK-6 is involved in the mechanism by which estrogen and oocytes synergistically augment FSH activity in granulosa cells.
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
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created: July 25, 2004, 9:40 a.m. by: hsueh   email:
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last update: April 17, 2013, 1:35 p.m. by: hsueh    email:



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