PMID- 8702581
OWN - NLM
STAT- MEDLINE
DCOM- 19960916
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 32
DP  - 1996 Aug 9
TI  - The amino-terminal extracellular domain of the MCP-1 receptor, but not the 
      RANTES/MIP-1alpha receptor, confers chemokine selectivity. Evidence for a 
      two-step mechanism for MCP-1 receptor activation.
PG  - 19084-92
AB  - The chemoattractant cytokines, MCP-1 (monocyte chemoattractant protein) and 
      MIP-1alpha (macrophage inflammatory protein), are recognized by highly homologous 
      but distinct receptors. To identify receptor domains involved in determining 
      ligand specificity, we created a series of chimeric MCP-1 and RANTES (regulated 
      on activation, normal T cell expressed and secreted)/MIP-1alpha receptors that 
      progressively interchanged the amino terminus and each of the three extracellular 
      loops. Radiolabeled MCP-1 bound with high affinity to the wild-type MCP-1 
      receptor, but not to the RANTES/MIP-1alpha receptor (C-C CKR-1). Chimeras that 
      retained the amino-terminal extension of the MCP-1 receptor bound MCP-1 with high 
      affinity. In contrast, chimeric MCP-1 receptors, in which the wild-type amino 
      terminus was replaced with the corresponding portion of the RANTES/MIP-1alpha 
      receptor, bound MCP-1 with low affinity. These data indicate that the amino 
      terminus of the MCP-1 receptor is necessary for high affinity binding of the 
      ligand. Very different results were obtained using the RANTES/MIP-1alpha 
      receptor. Radiolabeled MIP-1alpha bound with high affinity to chimeras that 
      expressed the extracellular loops of the RANTES/MIP-1alpha receptor. In contrast 
      to the MCP-1 receptor, substitution of the wild-type amino-terminal extension had 
      little or no effect on MIP-1alpha binding. For the MCP-1, but not the 
      RANTES/MIP-1alpha receptor, the presence of the wild-type amino terminus also 
      significantly lowered the ligand concentration required for maximal signaling. We 
      conclude that the amino-terminal extension of the MCP-1 receptor, but not the 
      RANTES/MIP-1alpha receptor, is critically involved in ligand binding and signal 
      transduction. These data reveal significant functional differences between the 
      two C-C chemokine receptors and suggest a two-step mechanism for activation of 
      the MCP-1 receptor.
FAU - Monteclaro, F S
AU  - Monteclaro FS
AD  - Gladstone Institute of Cardiovascular Disease, University of California San 
      Francisco, California 94141-9100, USA.
FAU - Charo, I F
AU  - Charo IF
LA  - eng
GR  - HL52773/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Cytokine)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (macrophage inflammatory protein 1alpha receptor)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Chemokines/*metabolism
MH  - Humans
MH  - Protein Binding
MH  - Receptors, CCR2
MH  - Receptors, CCR5
MH  - *Receptors, Chemokine
MH  - Receptors, Cytokine/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Signal Transduction
EDAT- 1996/08/09 00:00
MHDA- 1996/08/09 00:01
CRDT- 1996/08/09 00:00
PHST- 1996/08/09 00:00 [pubmed]
PHST- 1996/08/09 00:01 [medline]
PHST- 1996/08/09 00:00 [entrez]
AID - S0021-9258(19)84332-6 [pii]
AID - 10.1074/jbc.271.32.19084 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Aug 9;271(32):19084-92. doi: 10.1074/jbc.271.32.19084.