Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha.
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.
Raport
C J
CJ
ICOS Corporation, Bothell, Washington 98021, USA.
Gosling
J
J
Schweickart
V L
VL
Gray
P W
PW
Charo
I F
IF
D000595:Amino Acid Sequence; D001483:Base Sequence; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism*; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D015723:Gene Library; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008969:Molecular Sequence Data; D015846:Monokines / Q000378:metabolism*; D005810:Multigene Family; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D017931:DNA Primers; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019713:Receptors, CCR5; D018121:Receptors, Cytokine