MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF MURINE JE (MONOCYTE CHEMOATTRACTANT PROTEIN-1) AND MURINE MACROPHAGE INFLAMMATORY PROTEIN LARECEPTORS - EVIDENCE FOR 2 CLOSELY LINKED C-C CHEMOKINE RECEPTORS ON CHROMOSOME-9

We have isolated cDNA clones that encode two closely related, murine C -C chemokine receptors, Both receptors are members of the G-protein co upled, seven-transmembrane domain family of receptors and are most clo sely related to the human monocyte chemoattractant protein 1 receptor. Expression of each of the receptors was detected in murine monocyte/m acrophage cell lines, but not in nonhematopoietic lines, Expression of these receptors in Xenopus oocytes revealed that one receptor signale d in response to low nanomolar concentrations of murine JE, whereas th e second receptor was activated by murine macrophage inflammatory prot ein (MIP) 1 alpha and the human chemokines MIP-1 beta and RANTES. Bind ing studies revealed high affinity binding of radiolabeled mJE to the mJE receptor and murine MIP-1 alpha to the second receptor. Chromosoma l localization indicated that the two receptor genes were clustered wi thin 80 kilobases of each other on mouse chromosome 9. Creation of rec eptor chimeras suggested that the amino terminus was critically involv ed in mediating signal transduction and ligand specificity of the mJE receptor, but not the mMIP-1 alpha receptor, The identification and cl oning of two functional murine chemokine receptors provides important new tools for investigating the roles of these potent cytokines in viv o.