Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR.

The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow, GB.

We report here the identification and characterization of murine CCX-CKR, a high affinity receptor for the murine beta-chemokines SLC/mCCL21, MIP-3beta/mCCL19 and TECK/mCCL25. Unlike most other chemokine receptors, CCX-CKR is unable to mediate Ca(2+) fluxes upon ligand binding when expressed in HEK293 cells. Murine CCX-CKR is expressed predominantly in the heart and lung, but is detectable in most organs using RT-PCR. Interestingly, in brain and testis, an alternative mRNA form of CCX-CKR exists with a unique 5' untranslated region (5'UTR) that overlaps with a novel acyl-CoA dehydrogenase (ACD) gene. Analysis of human CCX-CKR shows that the expression profiles and alternative 5'UTR are conserved. However, in man, there are two copies of the CCX-CKR gene, one on chromosome 3 nestled within the ACD homologue, and one on chromosome 6. These genes encode proteins with only one amino acid difference, and their expression is independently regulated.This study identifies murine CCX-CKR, reveals complex regulation of CCX-CKR gene expression in mouse and man, and is suggestive of non-leukocytic targets for MIP-3beta/CCL19, SLC/CCL21 and TECK/CCL25.

PMID: 11981810 [PubMed - indexed for MEDLINE]