Cloning and functional expression of CC CKR5, a human monocytg CC chemokine receptor selective for MIP-1α, MIP-1β, and RANTES

Christophe Combadiere, Sunil K Ahuja, H. Lee Tiffany, Philip M. Murphy

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

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-1α (MIP-1α), MIP-1β, 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 ~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-1α, MIP-1β, and RANTES.

Original languageEnglish (US)
Pages (from-to)147-152
Number of pages6
JournalJournal of Leukocyte Biology
Volume60
Issue number1
StatePublished - Jul 1996

Fingerprint

CCR Receptors
CCR5 Receptors
Macrophage Inflammatory Proteins
Chemokine CCL5
Organism Cloning
Monocytes
Calcium
HEK293 Cells
Pertussis Toxin
Chemokines
Eosinophils
Inhibitory Concentration 50
Neutrophils
Complementary DNA
Amino Acids
Messenger RNA

Keywords

  • Chemotaxis
  • G protein
  • Inflammation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cloning and functional expression of CC CKR5, a human monocytg CC chemokine receptor selective for MIP-1α, MIP-1β, and RANTES. / Combadiere, Christophe; Ahuja, Sunil K; Tiffany, H. Lee; Murphy, Philip M.

In: Journal of Leukocyte Biology, Vol. 60, No. 1, 07.1996, p. 147-152.

Research output: Contribution to journalArticle

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AU - Tiffany, H. Lee

AU - Murphy, Philip M.

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N2 - 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-1α (MIP-1α), MIP-1β, 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 ~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-1α, MIP-1β, and RANTES.

AB - 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-1α (MIP-1α), MIP-1β, 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 ~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-1α, MIP-1β, and RANTES.

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