RGD Reference Report - Endogenous G protein-coupled receptor kinase 6 triggers homologous beta-adrenergic receptor desensitization in primary uterine smooth muscle cells. - Rat Genome Database

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Endogenous G protein-coupled receptor kinase 6 triggers homologous beta-adrenergic receptor desensitization in primary uterine smooth muscle cells.

Authors: Simon, V  Robin, MT  Legrand, C  Cohen-Tannoudji, J 
Citation: Simon V, etal., Endocrinology 2003 Jul;144(7):3058-66.
RGD ID: 1299124
Pubmed: PMID:12810562   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2002-0138   (Journal Full-text)

We previously reported that G protein-coupled receptor kinase (GRK) may contribute to beta-adrenergic receptor (beta-AR) uncoupling occurring just before parturition in rat uterine muscle (myometrium). To identify the GRK involved, we set up in this study a primary cell culture retaining the morphological and functional characteristics of myometrial tissue as well as the in vivo pattern of GRK expression (GRK2, GRK5, and GRK6). In this model, homologous beta-AR desensitization was assessed by an approximately 60% decrease in cAMP production to a subsequent challenge with the beta-agonist, isoproterenol. Desensitization was reduced by 36% with a GRK inhibitor, heparin, and by 31% with a protein kinase A in-hibitor, H89. Using antibodies known to specifically inhibit either GRK2/3 or GRK4-6 families, we demonstrated that only the GRK4-6 family mediated beta-AR desensitization. To discriminate between endogenous GRK5 and GRK6, we attempted to inhibit their action by introducing, into myometrial cells, kinase-dead dominant-negative mutants ((K215R)GRK5 and (K215R)GRK6). Expression of (K215R)GRK6 increased by approximately 70% the cAMP response to isoproterenol without effect on forskolin stimulation. Conversely, expression of (K215R)GRK5 or (K220R)GRK2 had no effect on beta-adrenergic signaling. These results strongly suggest that endogenous GRK6 mediate homologous beta-AR desensitization in myometrial cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grk6Ratdesensitization of G protein-coupled receptor signaling pathway  IDA  RGD 
Grk6Ratprotein phosphorylation  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grk6RatG protein-coupled receptor kinase activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Grk6  (G protein-coupled receptor kinase 6)

Objects referenced in this article
Gene Grk5 G protein-coupled receptor kinase 5 Rattus norvegicus

Additional Information