Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line.
We report the cloning and characterization of a novel basophil CC chemokin receptor, K5-5, from the human immature basophilic cell line KU-812. The predicted protein sequence of K5-5 shows only 49% identity to the macrophage inflammatory protein-1 alpha/RANTES receptor (CC CKR-1) and 47% identity to monocyte chemotactic protein-1 receptor (b form), suggesting that this cDNA encodes a novel member of the CC chemokine receptor family. Analysis of K5-5 mRNA expression indicates that it is restricted to leukocyte-rich tissues. In addition, we have shown significant levels of K5-5 mRNA in human basophils, which were up-regulated by treatment with interleukin-5. The CC chemokines, Macrophage inflammatory protein-1 alpha, RANTES, and monocyte chemotactic protein-1 were able to stimulate a Ca(2+)-activated chloride channel in Xenopus laevis oocytes injected with K5-5 cRNA, whereas no signal was detected in response to monocyte chemotactic protein-2, macrophage inflammatory protein-1 beta, or the CXC chemokine, interleukin-8. Taken together, these results indicate for the first time the presence of a CC chemokine receptor on basophils, which functions as a "shared" CC chemokine receptor and may therefore be implicated in the pathogenesis of basophil-mediated allergic diseases.
Power
C A
CA
Glaxo Institute for Molecular Biology, Plan-les-Ouates, Geneva, Switzerland.
Meyer
A
A
Nemeth
K
K
Bacon
K B
KB
Hoogewerf
A J
AJ
Proudfoot
A E
AE
Wells
T N
TN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001491:Basophils / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
C515354:CCR4 protein, human; D018076:DNA, Complementary; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine