Structure and function of the murine chemokine receptor CXCR3

The gene encoding the murine homologue of human CXCR3 exists in a single co py consisting of two exons with an intron interrupting the coding sequence between nucleotides 10 and 11. The deduced amino acid sequence is 86% ident ical to the predicted human sequence. Murine CXCR3 mRNA is detectable in bo ne marrow cells cultured in the presence of IL-2 but not unstimulated cells . It is also detectable at low abundance in normal mouse spleen, lymph node , mammary gland, and thymus. Transfection of murine CXCR3 in murine pre-B l ymphocyte line (CXCR3/L1.2) conferred binding of the ligands IP10, ITAC and Mig with K-D's of 1.35 +/- 0.56, 1.41 +/- 0.20, and 11.65 +/- 0.90 nM, res pectively. Lower affinity binding was observed for several beta or CC chemo kines (eotaxin, MCP-3, MIP3 alpha and SLC/6Ckine/Exodus 2). ITAC, IP10 and Mig induced chemotaxis with an order of potency ITAC > IP10 = Mig. The chem okines also increased intracellular calcium concentration and were variably desensitized to repeated agonist stimulation. The hierarchy for cross-dese nsitization was ITAC > Mig > IP10. Thus, while Mig, ITAC and IP10 all act o n the same receptor for binding and agonist stimulation, they may interact with different receptor conformational isoforms to produce divergent respon ses.