PMID- 8663314 OWN - NLM STAT- MEDLINE DCOM- 19960912 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 271 IP - 29 DP - 1996 Jul 19 TI - Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. PG - 17161-6 AB - Chemokines affect leukocyte chemotactic and activation activities through specific G protein-coupled receptors. In an effort to map the closely linked CC chemokine receptor genes, we identified a novel chemokine receptor encoded 18 kilobase pairs downstream of the monocyte chemoattractant protein-1 (MCP-1) receptor (CCR2) gene on human chromosome 3p21. The deduced amino acid sequence of this novel receptor, designated CCR5, is most similar to CCR2B, sharing 71% identical residues. Transfected cells expressing the receptor bind RANTES (regulated on activation normal T cell expressed), MIP-1beta, and MIP-1alpha with high affinity and generate inositol phosphates in response to these chemokines. This same combination of chemokines has recently been shown to potently inhibit human immunodeficiency virus replication in human peripheral blood leukocytes (Cocchi, F., DeVico, A. L., Garzino-Demo, A., Arya, S. K., Gallo, R. C., and Lusso, P.(1995) Science 270, 1811-1815). CCR5 is expressed in lymphoid organs such as thymus and spleen, as well as in peripheral blood leukocytes, including macrophages and T cells, and is the first example of a human chemokine receptor that signals in response to MIP-1beta. FAU - Raport, C J AU - Raport CJ AD - ICOS Corporation, Bothell, Washington 98021, USA. FAU - Gosling, J AU - Gosling J FAU - Schweickart, V L AU - Schweickart VL FAU - Gray, P W AU - Gray PW FAU - Charo, I F AU - Charo IF LA - eng SI - GENBANK/U54994 GR - HL52773/HL/NHLBI NIH HHS/United States PT - Comparative Study 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 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (Chemokine CCL5) RN - 0 (DNA Primers) RN - 0 (Growth Inhibitors) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Monokines) RN - 0 (Receptors, CCR5) RN - 0 (Receptors, Cytokine) SB - IM MH - Amino Acid Sequence MH - Base Sequence MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Chemokine CCL5/*metabolism MH - Chromosome Mapping MH - Chromosomes, Artificial, Yeast MH - *Chromosomes, Human, Pair 3 MH - Cloning, Molecular MH - DNA Primers MH - Female MH - Gene Library MH - Growth Inhibitors/metabolism MH - Humans MH - Kinetics MH - Macrophage Inflammatory Proteins MH - Male MH - Molecular Sequence Data MH - Monokines/*metabolism MH - Multigene Family MH - Organ Specificity MH - Polymerase Chain Reaction MH - Receptors, CCR5 MH - Receptors, Cytokine/chemistry/genetics/*metabolism MH - Restriction Mapping MH - Sequence Homology, Amino Acid EDAT- 1996/07/19 00:00 MHDA- 1996/07/19 00:01 CRDT- 1996/07/19 00:00 PHST- 1996/07/19 00:00 [pubmed] PHST- 1996/07/19 00:01 [medline] PHST- 1996/07/19 00:00 [entrez] AID - S0021-9258(18)31312-7 [pii] AID - 10.1074/jbc.271.29.17161 [doi] PST - ppublish SO - J Biol Chem. 1996 Jul 19;271(29):17161-6. doi: 10.1074/jbc.271.29.17161.