MOLECULAR-CLONING OF MURINE CC-CKR-4 AND HIGH-AFFINITY BINDING OF CHEMOKINES TO MURINE AND HUMAN CC-CKR-4

We have cloned the murine homologue of human CC Chemokine Receptor-4 ( CC CKR-4). In equilibrium competition binding assays performed in undi fferentiated HL-60 cells transfected with human and murine CC CKR-4 cD NA, the IC50 values for the binding of [I-125]macrophage inflammatory protein-lot to human and murine CC CKR-4 were 14.5 +/- 9.0 nM and 10.1 +/- 3.0 nM, respectively, and the IC50 values for the binding of [(12 5)]RANTES to human and murine CC CKR-4 were 9.3 +/- 3.0 nM and 5.7 +/- 2.6 nM, respectively. The cDNA clone for murine CC CKR-4 is 1531 bp, and the largest open reading frame encodes a protein of 360 amino acid s that is 85% identical to human CC CKR-4. Murine CC CKR-4 was detecte d in the thymus and T-cell lines by Northern blot analysis. This first report of direct binding of chemokines to CC CKR-4 demonstrates that the highly homologous human and murine receptors have similar binding characteristics and tissue distribution. (C) 1996 Academic Press, Inc.