PMID- 10094932
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20190516
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 13
IP  - 6
DP  - 1999 Apr
TI  - Decreased expression and activity of G-protein-coupled receptor kinases in
      peripheral blood mononuclear cells of patients with rheumatoid arthritis.
PG  - 715-25
AB  - 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.
FAU - Lombardi, M S
AU  - Lombardi MS
AD  - Department of Immunology, University Hospital for Children and Youth, 'Het
      Wilhelmina Kinderziekenhuis', 3584 EA Utrecht, The Netherlands.
      s.lombardi@wkz.azu.nl
FAU - Kavelaars, A
AU  - Kavelaars A
FAU - Schedlowski, M
AU  - Schedlowski M
FAU - Bijlsma, J W
AU  - Bijlsma JW
FAU - Okihara, K L
AU  - Okihara KL
FAU - Van de Pol, M
AU  - Van de Pol M
FAU - Ochsmann, S
AU  - Ochsmann S
FAU - Pawlak, C
AU  - Pawlak C
FAU - Schmidt, R E
AU  - Schmidt RE
FAU - Heijnen, C J
AU  - Heijnen CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Arrestins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (beta-Arrestins)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases)
RN  - EC 2.7.11.16 (G-Protein-Coupled Receptor Kinase 5)
RN  - EC 2.7.11.16 (G-Protein-Coupled Receptor Kinases)
RN  - EC 2.7.11.16 (G-protein-coupled receptor kinase 6)
RN  - EC 2.7.11.16 (GRK5 protein, human)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - N8ONU3L3PG (Terbutaline)
SB  - IM
MH  - Adrenergic beta-Agonists/pharmacology
MH  - Adult
MH  - Aged
MH  - Arrestins/biosynthesis
MH  - Arthritis, Rheumatoid/*enzymology
MH  - Cyclic AMP/analysis
MH  - Cyclic AMP-Dependent Protein Kinases/biosynthesis/genetics
MH  - Female
MH  - G-Protein-Coupled Receptor Kinase 5
MH  - G-Protein-Coupled Receptor Kinases
MH  - *GTP-Binding Proteins
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Middle Aged
MH  - Monocytes/*enzymology
MH  - Protein Kinases/*biosynthesis
MH  - *Protein-Serine-Threonine Kinases
MH  - RNA, Messenger/analysis
MH  - Receptor Protein-Tyrosine Kinases/biosynthesis/genetics
MH  - Receptors, Adrenergic, beta-2/metabolism
MH  - Signal Transduction
MH  - Terbutaline/pharmacology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - beta-Adrenergic Receptor Kinases
MH  - beta-Arrestins
EDAT- 1999/03/30 00:00
MHDA- 1999/03/30 00:01
CRDT- 1999/03/30 00:00
PHST- 1999/03/30 00:00 [pubmed]
PHST- 1999/03/30 00:01 [medline]
PHST- 1999/03/30 00:00 [entrez]
AID - 10.1096/fasebj.13.6.715 [doi]
PST - ppublish
SO  - FASEB J. 1999 Apr;13(6):715-25. doi: 10.1096/fasebj.13.6.715.