Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES.
We have cloned a human cDNA for a novel CC chemokine receptor (CC CKR) designated CC CKR5 that has 48-75% amino acid identity to other CC CKRs. CC CKR5 mRNA was detected constitutively in primary adherent monocytes but not in primary neutrophils or eosinophils. Macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES were all potent agonists for CC CKR5 (EC50 = 3-30 nM) when calcium flux was measured in transfected HEK 293 cells, yet the apparent binding affinities of the corresponding iodinated chemokines to intact cells expressing the receptor were low (IC50 approximately 100 nM). The calcium flux responses were completely blocked by treatment of transfected cells with pertussis toxin. These data suggest that CC CKR5 is a G(i)-coupled receptor that may mediate monocyte responses to MIP-1alpha, MIP-1beta, and RANTES.
Combadiere
C
C
The Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ahuja
S K
SK
Tiffany
H L
HL
Murphy
P M
PM
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D003001:Cloning, Molecular; D015870:Gene Expression; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007668:Kidney; D007962:Leukocytes / Q000502:physiology; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D015846:Monokines / Q000378:metabolism / Q000494:pharmacology*; D037342:Pertussis Toxin; D011869:Radioligand Assay; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D002118:Calcium