MOLECULAR-CLONING AND EXPRESSION OF A NOVEL RAT CC-CHEMOKINE RECEPTOR(RCCR10RR) THAT BINDS MCP-1 AND MIP-1-BETA WITH HIGH-AFFINITY

Chemokines stimulate the migration and activation of leukocytes to are as of inflammation or tissue damage by binding to specific seven-trans membrane G protein-coupled receptors, We report the cloning of a novel rat CC-chemokine receptor, the rat CCR10-related receptor (rCCR10rR), with 72% amino acid identity to the human CC-chemokine receptor CCR10 and 30%-35% amino acid identity to the known human CC-chemokine recep tors CCR1, CCR2, CCR3, CCR4 and CCR5, Multiple tissue northern analysi s indicates that rCCR10rR is expressed at a higher level in spleen tha n in the other tissues assayed, The CC-chemokines MIP-1 beta and MCP-1 bind with highest affinity to rCCR10rR, with K-D = 0.4 and 0.7 nM, re spectively, The CC-chemokines RANTES and MIP-1 alpha were poor competi tors for MIP-1 beta binding, with IC50 values of 150 nM and 86 nM, res pectively, but the K-D for RANTES binding was still in the nanamolar r ange (4.8 nM), These results indicate that rCCR10rR is a true member o f the CC-chemokine receptor family and may be involved in eliciting th e responses to the CC-chemokines MIP-1 beta and MCP-1.