Structure and functional expression of the human macrophage inflammatory protein 1α/RANTES receptor

Abstract

The chemokine β family is comprised of at least six distinct cytokines that regulate trafficking of phagocytes and lymphocytes in mammalian species; at least one of these, macrophage inflammatory protein 1α (MIP-1α), also regulates the growth of hematopoietic stem cells. We now show that MIP-1α and the related β chemokine, RANTES, induce transient alterations in intracellular Ca2+ concentration in polymorphonuclear leukocytes that can be reciprocally and specifically desensitized, suggesting a common receptor. Moreover, we have now cloned both the cDNA and the gene for this receptor, functionally expressed the receptor in Xenopus oocytes, and mapped the gene to human chromosome 3p21. Transcripts for the receptor were found in mature and immature myeloid cells as well as B cells. The receptor is a member of the G protein-coupled receptor superfamily. It has ∼33% amino acid identity with receptors for the α chemokine, interleukin 8, and may be the human homologue of the product of US28, an open reading frame of human cytomegalovirus.