CLONING, CHROMOSOMAL LOCALIZATION, AND RNA EXPRESSION OF A HUMAN BETACHEMOKINE RECEPTOR-LIKE GENE

A human cDNA encoding a putative G protein-coupled receptor designated chemokine beta receptor-like 1 (CMKBRL1) was isolated from an eosinop hilic leukemia library. Its deduced sequence is similar to 40% identic al to previously cloned receptors for the beta chemokines macrophage i nflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemoa ttractant protein-1 (MCP-1), which are chemoattractants for blood leuk ocytes, and is 83% identical to the product of the orphan rat cDNA RES 11, Like the MIP-1 alpha/RANTES receptor, CMKBRL1 is encoded by a sma ll, single-copy gene that maps to chromosome 3p21 and is expressed in leukocytes, However, two screening assays with a broad panel of chemok ines failed to identify its ligand, CMKBRL1 mRNA was detectable by Nor thern blot hybridization in neutrophils and monocytes, hut not eosinop hils, and was also found in eight solid organs that were tested with p articularly high expression in brain, The RNA distribution of the know n beta chemokine receptors was overlapping but distinct from that of C MKBRL1. MIP-1 alpha/RANTES receptor mRNA was detectable in neutrophils , monocytes, eosinophils, and in all eight solid organs tested, with p articularly high expression in placenta, lung, and Ever, MCP-1 recepto r mRNA was found in monocytes, lung, liver, and pancreas, These result s suggest that the ligand for the putative CMKBRRL1 receptor is a beta chemokine that targets both neutrophils and monocytes, Moreover, the RNA distributions suggest that CMKBRL1, the MIP-1 alpha/RANTES recepto r, and the MCP-1 receptor may have both overlapping and distinct biolo gical roles.