Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6.

Members of the chemokine family of chemotactic peptides interact with their target cells through heptahelical cell surface receptors. An understanding of the biochemistry and expression patterns of these receptors is therefore central to our overall understanding of the roles played by chemokines in both physiological and pathological processes. To date, eight receptors for the beta-chemokine subfamily have been described. We have recently cloned a novel murine beta-chemokine receptor and report here the identification and characterization of a highly homologous human gene termed human D6 (hD6). This is a promiscuous beta-chemokine receptor and appears to be able to bind the majority of members of the beta-chemokine family. It is, however, specific for this family and shows no detectable affinity for members of the alpha-chemokine or the C or CXXXC chemokines. Unlike the majority of other chemokine receptors, human D6 does not appear to be able to flux calcium following ligand binding, thus it is currently not clear if this novel receptor is indeed a signaling receptor. Human D6 is expressed in a range of tissues including hemopoietic cells although it appears not to be ubiquitously expressed in hemopoietic cells. Human D6, unlike some other beta-chemokine receptors, appears not to be able to function as an entry co-factor for human immunodeficiency virus type 1 (HIV-)1 on CD4-expressing cells.