Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP‐1α, MIP‐1β, 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‐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 Gi‐coupled receptor that may mediate monocyte responses to MIP‐1α, MIP‐1β, and RANTES.

[1]  C. Combadière,et al.  Molecular Cloning of Human Eotaxin, an Eosinophil-selective CC Chemokine, and Identification of a Specific Eosinophil Eotaxin Receptor, CC Chemokine Receptor 3 (*) , 1996, The Journal of Biological Chemistry.

[2]  G Vassart,et al.  Molecular cloning and functional expression of a new human CC-chemokine receptor gene. , 1996, Biochemistry.

[3]  W Newman,et al.  Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. , 1996, The Journal of clinical investigation.

[4]  J. Van Damme,et al.  Monocyte Chemoattractant Protein-3 Is a Functional Ligand for CC Chemokine Receptors 1 and 2B (*) , 1995, The Journal of Biological Chemistry.

[5]  S. Arya,et al.  Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells , 1995, Science.

[6]  C. Power,et al.  Molecular Cloning and Functional Expression of a Novel CC Chemokine Receptor cDNA from a Human Basophilic Cell Line (*) , 1995, The Journal of Biological Chemistry.

[7]  C. Combadière,et al.  Cloning and Functional Expression of a Human Eosinophil CC Chemokine Receptor (*) , 1995, The Journal of Biological Chemistry.

[8]  B. Mouillac,et al.  Palmitoylation of G-protein-coupled receptors: a dynamic modification with functional consequences. , 1995, Biochemical Society transactions.

[9]  S. Coughlin,et al.  Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Hsuan,et al.  Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation , 1994, The Journal of experimental medicine.

[11]  A. Minty,et al.  Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine , 1994, The Journal of experimental medicine.

[12]  B. Dewald,et al.  Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. , 1994, Advances in immunology.

[13]  P. Murphy.  The molecular biology of leukocyte chemoattractant receptors. , 1994, Annual review of immunology.

[14]  Melvin I. Simon,et al.  G protein-coupled signal transduction pathways for interleukin-8. , 1993, Science.

[15]  D. Kelvin,et al.  Human recombinant macrophage inflammatory protein-1 alpha and -beta and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes. , 1993, Journal of immunology.

[16]  D. Kelvin,et al.  Identification of RANTES receptors on human monocytic cells: competition for binding and desensitization by homologous chemotactic cytokines , 1993, The Journal of experimental medicine.

[17]  H. Rosen,et al.  Characterization and species distribution of high affinity GTP-coupled receptors for human rantes and monocyte chemoattractant protein 1 , 1993, The Journal of experimental medicine.

[18]  T. Schall,et al.  Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor , 1993, Cell.

[19]  G. Opdenakker,et al.  Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family , 1992, The Journal of experimental medicine.

[20]  D. Dunlop,et al.  Demonstration of stem cell inhibition and myeloprotective effects of SCI/rhMIP1 alpha in vivo. , 1992, Blood.

[21]  M. Krangel,et al.  The human cytokine I-309 is a monocyte chemoattractant. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P. Murphy,et al.  Cloning of complementary DNA encoding a functional human interleukin-8 receptor. , 1991, Science.

[23]  W I Wood,et al.  Structure and functional expression of a human interleukin-8 receptor. , 1991, Science.

[24]  D. Goeddel,et al.  Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES , 1990, Nature.

[25]  E. Appella,et al.  Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. , 1989, Journal of immunology.

[26]  M. Kozak.  Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. , 1984, Nucleic acids research.