Cloning and differential tissue-specific expression of three mouse beta chemokine receptor-like genes, including the gene for a functional macrophage inflammatory protein-1 alpha receptor.
Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and RANTES, members of the beta chemokine family of leukocyte chemoattractants, bind to a common seven-transmembrane-domain human receptor. We have now cloned three related mouse genes: one for a selective MIP-1 alpha receptor (MIP-1 alpha R) and two for orphan receptors provisionally designated MIP-1 alpha receptor-like 1 and 2 (MIP-1 alpha RL1 and 2). Their deduced sequences are 80, 62, and 63% identical to the human MIP-1 alpha/RANTES receptor, respectively. K562 cells stably transfected with MIP-1 alpha R specifically bound 125I-human MIP-1 alpha and 125I-human RANTES with high affinity. The rank order of beta chemokine competition for 125I-human MIP-1 alpha binding was human MIP-1 alpha > mouse MIP-1 alpha approximately RANTES approximately MIP-1 beta > MCP-1. However, human RANTES was approximately 100-fold less potent as a calcium-mobilizing agonist for MIP-1 alpha R than either human or mouse MIP-1 alpha, which matched the selectively of mouse leukocytes for calcium mobilization by MIP-1 alpha and RANTES. No other beta or alpha chemokines tested were agonists for MIP-1 alpha R. RNA for all three genes was detected in mouse leukocytes, but unique patterns of expression were identified in solid organs: MIP-1 alpha R, heart, spleen, and lung; MIP-1 alpha RL1, skeletal muscle; and MIP-1 alpha RL2, spleen and liver. These data identify potentially important new targets for beta chemokine action in the mouse.
Gao
J L
JL
Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
Murphy
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015846:Monokines / Q000378:metabolism; D009928:Organ Specificity; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic / Q000235:genetics*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; C080633:macrophage inflammatory protein 1alpha receptor