Molecular cloning and expression of a novel rat CC-chemokine receptor (rCCR10rR) that binds MCP-1 and MIP-1beta with high affinity.
Chemokines stimulate the migration and activation of leukocytes to areas of inflammation or tissue damage by binding to specific seven-transmembrane G protein-coupled receptors. We report the cloning of a novel rat CC-chemokine receptor, the rat CCR10-related receptor (rCCR10rR), with 72% amino acid identity to the human CC-chemokine receptor CCR10 and 30%-35% amino acid identity to the known human CC-chemokine receptors CCR1, CCR2, CCR3, CCR4, and CCR5. Multiple tissue northern analysis indicates that rCCR10rR is expressed at a higher level in spleen than in the other tissues assayed. The CC-chemokines MIP-1beta and MCP-1 bind with highest affinity to rCCR10rR, with K(D) = 0.4 and 0.7 nM, respectively. The CC-chemokines RANTES and MIP-1alpha were poor competitors for MIP-1beta binding, with IC50 values of 150 nM and 86 nM, respectively, but the K(D) for RANTES binding was still in the nanamolar range (4.8 nM). These results indicate that rCCR10rR is a true member of the CC-chemokine receptor family and may be involved in eliciting the responses to the CC-chemokines MIP-1beta and MCP-1.
Bonini
J A
JA
The Howard Hughes Medical Institute and the Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637, USA.
Steiner
D F
DF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D018932:Chemokine CCL2 / Q000378:metabolism*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003001:Cloning, Molecular; D015870:Gene Expression; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000737:chemistry; D000097628:Chemokine Receptor D6
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; C515710:Ackr2 protein, rat; D000097628:Chemokine Receptor D6; C515706:CCR10 protein, human