PMID- 10477567
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20141120
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 6
DP  - 1999 Sep 15
TI  - Characterization of RANTES- and aminooxypentane-RANTES-triggered desensitization 
      signals reveals differences in recruitment of the G protein-coupled receptor
      complex.
PG  - 3037-44
AB  - The trafficking of lymphocyte populations is a complex process controlled by a
      vast array of molecules. In this process, cells must be able to sense small
      changes in chemoattractant gradients. Migration through a chemotactic gradient
      probably employs an on-off mechanism in which chemokine receptor desensitization,
      internalization, and recycling may be important steps. This multistep process
      requires the coordinated action of many factors, including G protein-coupled
      receptor kinases, arrestins, clathrin, and GTP-hydrolyzing proteins such as
      dynamin. In this report, we show that RANTES and its derivative, aminooxypentane 
      (AOP)-RANTES, a potent RANTES antagonist as well as an inhibitor of HIV-1
      infection, both promote CCR5 desensitization involving G protein-coupled receptor
      kinases-2 and beta-arrestin equally well. An important difference between the two
      molecules is that (AOP)-RANTES is more efficient than RANTES in promoting Ser/Thr
      phosphorylation of the receptor and association of G protein-coupled receptor
      kinases-2, beta-arrestin, and clathrin to the CCR5. After stimulation with either
      ligand, we observe rapid, transient association of dynamin to CCR5, implicating
      this protein in receptor sensitization, but this association is faster and
      longer-lasting following (AOP)-RANTES stimulation. In summary, we show that
      chemokine receptor internalization takes place through the formation of clathrin 
      vesicles and involves dynamin activity. We provide compelling evidence that the
      differences between RANTES and (AOP)-RANTES in G alpha i activation condition
      subsequent signaling events, including internalization and receptor recycling.
FAU - Vila-Coro, A J
AU  - Vila-Coro AJ
AD  - Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo 
      Superior de Investigaciones Cientificas/Universidad Autonoma de Madrid, Spain.
FAU - Mellado, M
AU  - Mellado M
FAU - Martin de Ana, A
AU  - Martin de Ana A
FAU - Martinez-A, C
AU  - Martinez-A C
FAU - Rodriguez-Frade, J M
AU  - Rodriguez-Frade JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Arrestins)
RN  - 0 (CCR5 Receptor Antagonists)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Clathrin)
RN  - 0 (Receptors, CCR5)
RN  - 0 (aminooxypentane-RANTES)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.5 (Dynamins)
SB  - AIM
SB  - IM
SB  - X
MH  - Arrestins/metabolism
MH  - CCR5 Receptor Antagonists
MH  - Chemokine CCL5/*analogs & derivatives/*physiology
MH  - Clathrin/metabolism
MH  - Coated Vesicles/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - *Desensitization, Immunologic
MH  - Down-Regulation/immunology
MH  - Dynamins
MH  - GTP Phosphohydrolases/metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Humans
MH  - Kinetics
MH  - Phosphorylation
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, CCR5/genetics/metabolism
MH  - Serine/metabolism
MH  - Signal Transduction/*immunology
MH  - Threonine/metabolism
MH  - Time Factors
MH  - Transfection
MH  - beta-Adrenergic Receptor Kinases
EDAT- 1999/09/08 00:00
MHDA- 1999/09/08 00:01
CRDT- 1999/09/08 00:00
PHST- 1999/09/08 00:00 [pubmed]
PHST- 1999/09/08 00:01 [medline]
PHST- 1999/09/08 00:00 [entrez]
AID - ji_v163n6p3037 [pii]
PST - ppublish
SO  - J Immunol. 1999 Sep 15;163(6):3037-44.