Structure and function of the murine chemokine receptor CXCR3.
The gene encoding the murine homologue of human CXCR3 exists in a single copy consisting of two exons with an intron interrupting the coding sequence between nucleotides 10 and 11. The deduced amino acid sequence is 86% identical to the predicted human sequence. Murine CXCR3 mRNA is detectable in bone 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 lymphocyte 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, respectively. Lower affinity binding was observed for several beta or CC chemokines (eotaxin, MCP-3, MIP3alpha and SLC/6Ckine/Exodus 2). ITAC, IP10 and Mig induced chemotaxis with an order of potency ITAC > IP10 = Mig. The chemokines also increased intracellular calcium concentration and were variably desensitized to repeated agonist stimulation. The hierarchy for cross- desensitization was ITAC > Mig > IP10. Thus, while Mig, ITAC and IP10 all act on the same receptor for binding and agonist stimulation, they may interact with different receptor conformational isoforms to produce divergent responses.
Lu
B
B
Ina Sue Perlmutter Laboratory Children's Hospital, Harvard Medical School, Boston, USA.
Humbles
A
A
Bota
D
D
Gerard
C
C
Moser
B
B
Soler
D
D
Luster
A D
AD
Gerard
N P
NP
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; D008024:Ligands; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine