PMID- 10085131
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 13
DP  - 1999 Mar 26
TI  - Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5)
      phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl 
      terminus.
PG  - 8875-85
AB  - The binding of CC chemokines to CC chemokine receptor 5 (CCR5) triggers cellular 
      responses that, generally, are only transient in nature. To explore the potential
      role of G protein-coupled receptor kinases (GRKs) in the regulation of CCR5, we
      performed phosphorylation experiments in a rat basophilic leukemia cell line
      stably expressing CCR5. The ability of various CCR5 ligands to stimulate calcium 
      mobilization in these cells correlated with their ability to induce receptor
      phosphorylation, desensitization, internalization, and GRK association with the
      receptor. Aminooxypentane-RANTES, a potent inhibitor of human immunodeficiency
      virus infection, has been proposed to act through enhanced CCR5 internalization
      and inhibition of receptor recycling. Aminooxypentane-RANTES profoundly induced
      CCR5 phosphorylation, but had no effect on CCR1. In permeabilized rat basophilic 
      leukemia CCR5 cells, monoclonal antibodies with specificity for GRK2/3 inhibited 
      RANTES-induced receptor phosphorylation. Consistent with a role for these kinases
      in CCR5 regulation, 1-2 x 10(5) copies of GRK2 or GRK3 were found to be expressed
      in peripheral blood leukocytes. Phosphoamino acid analysis revealed that
      RANTES-induced CCR5 phosphorylation selectively occurs on serine residues. Our
      findings with receptor mutants indicate that serine residues at positions 336,
      337, 342, and 349 represent GRK phosphorylation sites on CCR5. This study
      demonstrates that chemokines differ in their ability to induce CCR5
      phosphorylation and desensitization and provides a molecular mechanism for the
      agonist-induced attenuation of CCR5 signaling.
FAU - Oppermann, M
AU  - Oppermann M
AD  - Department of Immunology, University of Gottingen, 37075 Gottingen, Germany.
      mopperm@gwdg.de
FAU - Mack, M
AU  - Mack M
FAU - Proudfoot, A E
AU  - Proudfoot AE
FAU - Olbrich, H
AU  - Olbrich H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCR1 protein, human)
RN  - 0 (Ccr1 protein, rat)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines, CC)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Phosphoamino Acids)
RN  - 0 (Receptors, CCR1)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
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 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.15 (G-Protein-Coupled Receptor Kinase 3)
RN  - EC 2.7.11.15 (GRK3 protein, human)
RN  - EC 2.7.11.15 (Grk3 protein, rat)
RN  - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
SB  - X
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Chemokine CCL5/analogs & derivatives/pharmacology
MH  - Chemokines, CC/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - G-Protein-Coupled Receptor Kinase 3
MH  - Ligands
MH  - Mutation/genetics
MH  - Phosphoamino Acids/analysis
MH  - Phosphorylation
MH  - Protein Kinase C/antagonists & inhibitors
MH  - *Protein-Serine-Threonine Kinases
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, CCR1
MH  - Receptors, CCR5/*genetics/metabolism
MH  - Receptors, Chemokine/metabolism
MH  - Signal Transduction
MH  - beta-Adrenergic Receptor Kinases
EDAT- 1999/03/20 00:00
MHDA- 1999/03/20 00:01
CRDT- 1999/03/20 00:00
PHST- 1999/03/20 00:00 [pubmed]
PHST- 1999/03/20 00:01 [medline]
PHST- 1999/03/20 00:00 [entrez]
AID - 10.1074/jbc.274.13.8875 [doi]
AID - S0021-9258(19)87408-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 26;274(13):8875-85. doi: 10.1074/jbc.274.13.8875.