Molecular cloning and characterization of a cDNA, CHEMR1, encoding a chemokine receptor with a homology to the human C-C chemokine receptor, CCR-4.
Chemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites. These are known to bind to seven-transmembrane-domain containing receptors. A cDNA clone, CHEMR1, resembling the typical G protein-coupled receptor, was isolated from a mouse cytotoxic T-lymphocyte (CTL) library. Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells, including T cells, B cells, and macrophages. The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1alpha (MIP-1alpha) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside. Amino acid sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating that CHEMR1 is likely to be a mouse CCR-4. Binding assays using 125I-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1alpha, RANTES, or MIP-1beta, whereas CCR-1 binds MIP-1alpha and RANTES. Our result is different from the reported properties of human CCR-4. This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1alpha.
Youn
B S
BS
Department of Microbiology and Immunology, and Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
Kim
S H
SH
Lyu
M S
MS
Kozak
C A
CA
Taub
D D
DD
Kwon
B S
BS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D054414:Chemokine CCL17; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015723:Gene Library; D005796:Genes; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012260:Ribonucleases; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C106230:CCL17 protein, human; C515300:CCR1 protein, human; C499538:Ccl17 protein, mouse; C515301:Ccr1 protein, mouse; D054414:Chemokine CCL17; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D018076:DNA, Complementary; D005656:Fungal Proteins; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases