IDENTIFICATION OF SINGLE C-MOTIF-1 LYMPHOTACTIN RECEPTOR XCR1

Single C motif-1 (SCM-1)/lymphotactin is a member of the chemokine sup erfamily, but retains only the and and 4th of the four cysteine residu es conserved in other chemokines. In humans, there are two highly homo logous SCM-1 genes encoding SCM-1 alpha and SCM-1 beta with two amino acid substitutions. To identify a specific receptor for SCM-1 proteins , we produced recombinant SCM-1 alpha and SCM-1 beta by the baculoviru s expression system and tested them on murine L1.2 cells stably expres sing eight known chemokine receptors and three orphan receptors. Both proteins specifically induced migration in cells expressing an orphan receptor, GPR5. The migration was chemotactic and suppressed by pertus sis toxin, indicating coupling to a G alpha type of G protein. Both pr oteins also induced intracellular calcium mobilization in GPR5-express ing L1.2 cells with efficient mutual cross desensitization. SCM-1 alph a bound specifically to GPR5-expressing L1.2 cells with a K-d of 10 nM . By Northern blot analysis, GPR5 mRNA of about 5 kilobases was detect ed strongly in placenta and weakly in spleen and thymus among various human tissues. Identification of a specific receptor for SCM-1 would f acilitate our investigation on its biological function. Following the set rule for the chemokine receptor nomenclature, we propose to design ate GPR5 as XCR1 from XC chemokine receptor-1.