RGD Reference Report - Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis. - Rat Genome Database

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Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis.

Authors: Lombardi, MS  Kavelaars, A  Schedlowski, M  Bijlsma, JW  Okihara, KL  Van de Pol, M  Ochsmann, S  Pawlak, C  Schmidt, RE  Heijnen, CJ 
Citation: Lombardi MS, etal., FASEB J. 1999 Apr;13(6):715-25.
RGD ID: 5688380
Pubmed: PMID:10094932   (View Abstract at PubMed)

Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated with increased sensitivity to beta2-adrenergic activation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
rheumatoid arthritis  IEP 5688380; 5688380protein: decreased expression: mononuclear leukocytesRGD 
rheumatoid arthritis no_associationIEP 5688380protein: : mononuclear blood cellsRGD 
rheumatoid arthritis  ISOGRK2 (Homo sapiens)5688380; 5688380protein: decreased expression: mononuclear cellsRGD 
rheumatoid arthritis no_associationISOGRK5 (Homo sapiens)5688380; 5688380protein: decreased expression: mononuclear leukocytesRGD 
rheumatoid arthritis  ISOGRK6 (Homo sapiens)5688380; 5688380protein: decreased expression: mononuclear cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Grk2  (G protein-coupled receptor kinase 2)
Grk5  (G protein-coupled receptor kinase 5)
Grk6  (G protein-coupled receptor kinase 6)

Genes (Mus musculus)
Grk2  (G protein-coupled receptor kinase 2)
Grk5  (G protein-coupled receptor kinase 5)
Grk6  (G protein-coupled receptor kinase 6)

Genes (Homo sapiens)
GRK2  (G protein-coupled receptor kinase 2)
GRK5  (G protein-coupled receptor kinase 5)
GRK6  (G protein-coupled receptor kinase 6)


Additional Information