Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3.
Chemokines mediate their chemotactic, proinflammatory effects by binding to and activating a variety of specific receptors belonging to the G protein-coupled superfamily of seven-transmembrane serpentine receptors. We report the cloning, chromosomal localization, expression, and ligand binding of a novel CC chemokine receptor, CCR10. CCR10 is expressed primarily in placenta and fetal liver, and binds two of the CC chemokines, monocyte chemoattractant protein (MCP)-1 and MCP-3, with highest affinity. The KD for MCP-3 binding was 1 nM, and MCP-1 competed for MCP-3 binding with an IC50 of 1.2 nM. The CC chemokines MCP-4 and RANTES competed for MCP-3 binding with IC50 values of 7.5 and 5.4 nM, respectively. The chromosomal location of CCR10 was determined to coincide with the CC chemokine receptor cluster on chromosome 3 (3p21.31-3p21.32). These results indicate that CCR10 is a novel CC chemokine receptor with a unique expression pattern that would be consistent with a role in placental immunity or hematopoiesis.
Bonini
J A
JA
The Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, The University of Chicago, IL 60637, USA.
Martin
S K
SK
Dralyuk
F
F
Roe
M W
MW
Philipson
L H
LH
Steiner
D F
DF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D019556:COS Cells; D018932:Chemokine CCL2 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism; D054410:Chemokine CCL7; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003001:Cloning, Molecular; D016207:Cytokines; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
C515450:CCL7 protein, human; C515706:CCR10 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054447:Receptors, CCR10; D019707:Receptors, Chemokine