MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF 2 MONOCYTE CHEMOATTRACTANT PROTEIN-1 RECEPTORS REVEALS ALTERNATIVE SPLICING OF THE CARBOXYL-TERMINAL TAILS

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokin e family of cytokines that mediate leukocyte chemotaxis. The potent an d specific activation of monocytes by MCP-1 may mediate the monocytic infiltration of tissues in atherosclerosis and other inflammatory dise ases. We have isolated cDNAs that encode two MCP-1-specific receptors with alternatively spliced carboxyl tails. Expression of the receptors in Xenopus oocytes conferred robust mobilization of intracellular cal cium in response to nanomolar concentrations of MCP-1 but not to relat ed chemokines. The MCP-1 receptors are most closely related to the rec eptor for the chemokines macrophage inflammatory protein 1alpha and RA NTES (regulated on activation, normal T expressed and secreted). The i dentification of the MCP-1 receptor and cloning of two distinct isofor ms provide powerful tools for understanding the specificity and signal ing mechanisms of this important chemokine.