Cloning and Differential Tissue-specific Expression of Three Mouse β Chemokine Receptor-like Genes, Including the Gene for a Functional Macrophage Inflammatory Protein-1α Receptor

Macrophage inflammatory protein-1α (MIP-1α) and RANTES, members of the β 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-1α receptor (MIP-1αR) and two for orphan receptors provisionally designated MIP-1α receptor-like 1 and 2 (MIP-1αRL1 and 2). Their deduced sequences are 80, 62, and 63% identical to the human MIP-1α/RANTES receptor, respectively. K562 cells stably transfected with MIP-1αR specifically bound 125I-human MIP-1α and 125I-human RANTES with high affinity. The rank order of β chemokine competition for 125I-human MIP-1α binding was human MIP-1α > mouse MIP-1α∼ RANTES ∼ MIP-1β > MCP-1. However, human RANTES was ∼100-fold less potent as a calcium-mobilizing agonist for MIP-1αR than either human or mouse MIP-1α, which matched the selectivity of mouse leukocytes for calcium mobilization by MIP-1α and RANTES. No other β or α chemokines tested were agonists for MIP-1αR. RNA for all three genes was detected in mouse leukocytes, but unique patterns of expression were identified in solid organs: MIP-1αR, heart, spleen, and lung; MIP-1αRL1, skeletal muscle; and MIP-1αRL2, spleen and liver. These data identify potentially important new targets for β chemokine action in the mouse. Macrophage inflammatory protein-1α (MIP-1α) and RANTES, members of the β 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-1α receptor (MIP-1αR) and two for orphan receptors provisionally designated MIP-1α receptor-like 1 and 2 (MIP-1αRL1 and 2). Their deduced sequences are 80, 62, and 63% identical to the human MIP-1α/RANTES receptor, respectively. K562 cells stably transfected with MIP-1αR specifically bound 125I-human MIP-1α and 125I-human RANTES with high affinity. The rank order of β chemokine competition for 125I-human MIP-1α binding was human MIP-1α > mouse MIP-1α∼ RANTES ∼ MIP-1β > MCP-1. However, human RANTES was ∼100-fold less potent as a calcium-mobilizing agonist for MIP-1αR than either human or mouse MIP-1α, which matched the selectivity of mouse leukocytes for calcium mobilization by MIP-1α and RANTES. No other β or α chemokines tested were agonists for MIP-1αR. RNA for all three genes was detected in mouse leukocytes, but unique patterns of expression were identified in solid organs: MIP-1αR, heart, spleen, and lung; MIP-1αRL1, skeletal muscle; and MIP-1αRL2, spleen and liver. These data identify potentially important new targets for β chemokine action in the mouse. Cloning and differential tissue-specific expression of three mouse β chemokine receptor-like genes, including the gene for a functional macrophage inflammatory protein-1α receptor.Journal of Biological ChemistryVol. 271Issue 12PreviewVol. 270, p. 17494 Full-Text PDF Open Access Chemokines are structurally related 70-90-amino acid polypeptides whose most widely shared property is the ability to function as chemoattractants and activating factors for mammalian leukocytes (reviewed in (1Baggiolini M. Dewald B. Moser B. Adv. Immunol. 1994; 55: 97-179Crossref PubMed Scopus (2263) Google Scholar)). Chemokines form two subfamilies, α and β, based on the presence or absence of a single amino acid between the first two of four conserved cysteine residues. Most α chemokines attract and activate neutrophils, whereas all known β chemokines target monocytes but have little if any affect on neutrophils. The β chemokines macrophage inflammatory protein-1α (MIP-1α),1 1The abbreviations used are: MIPmacrophage inflammatory proteinkbkilobase(s) or kilobase pair(s)RANTESregulated on activation, normal T-expressed and secretedMCP-1monocyte chemoattractant protein-1fMLPN-formyl-methionyl-leucyl-phenylalanineG proteinheterotrimeric guanine nucleotide-binding regulatory proteinIL-8interleukin-8PCRpolymerase chain reactionORFopen reading frame. MIP-1β, RANTES, and monocyte chemoattractant protein-1 (MCP-1) also attract basophils, eosinophils, and lymphocytes with variable selectivity(1Baggiolini M. Dewald B. Moser B. Adv. Immunol. 1994; 55: 97-179Crossref PubMed Scopus (2263) Google Scholar, 2Baggiolini M. Dahinden C.A. Immunol. Today. 1994; 15: 127-133Abstract Full Text PDF PubMed Scopus (518) Google Scholar, 3Carr M.W. Roth S.J. Luther E. Rose S.S. Springer T.A. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 3652-3656Crossref PubMed Scopus (1042) Google Scholar, 4Schall T.J. Bacon K. Camp R.D. Kaspari J.W. Goeddel D.V. J. Exp. Med. 1993; 177: 1821-1826Crossref PubMed Scopus (497) Google Scholar, 5Taub D.D. Conlon K. Lloyd A.R. Oppenheim J.J. Kelvin D.J. Science. 1993; 260: 355-358Crossref PubMed Scopus (705) Google Scholar, 6Tanaka Y. Adams D.H. Hubscher S. Hirano H. Siebenlist U. Shaw S. Nature. 1993; 361: 79-82Crossref PubMed Scopus (846) Google Scholar). In addition, MIP-1α has been shown to suppress hematopoietic stem cell proliferation (7Graham G.J. Wright E.G. Hewick R. Wolpe S.D. Wilkie N.M. Donaldson D. Lorimore S. Pragnell I.B. Nature. 1990; 344: 442-444Crossref PubMed Scopus (392) Google Scholar, 8Maze R. Sherry B. Kwon B.S. Cerami A. Broxmeyer H.E. J. Immunol. 1992; 149: 1004-1009PubMed Google Scholar, 9Dunlop D.J. Wright E.G. Lorimore S. Graham G.J. Holyoake T. Kerr D.J. Wolpe S.D. Pragnell I.B. Blood. 1992; 79: 2221-2225Crossref PubMed Google Scholar, 10Cooper S. Mantel C. Broxmeyer H.E. Exp. Hematol. 1994; 22: 186-193PubMed Google Scholar). macrophage inflammatory protein kilobase(s) or kilobase pair(s) regulated on activation, normal T-expressed and secreted monocyte chemoattractant protein-1 N-formyl-methionyl-leucyl-phenylalanine heterotrimeric guanine nucleotide-binding regulatory protein interleukin-8 polymerase chain reaction open reading frame. Seventeen distinct human chemokines (10 α and 7 β) have been identified so far (reviewed in (1Baggiolini M. Dewald B. Moser B. Adv. Immunol. 1994; 55: 97-179Crossref PubMed Scopus (2263) Google Scholar) and (11Michiel D. Bio/Technology. 1993; 11: 739Crossref PubMed Scopus (5) Google Scholar)). One way to sort out the biological roles of each member of this complex system is by gene knockout technology in the mouse. However, the mouse chemokine system may differ fundamentally from the human system. For example, the human α chemokine interleukin-8 (IL-8) has no known counterpart in the mouse. Furthermore, only one mouse gene for an IL-8 receptor homologue has been found, whereas two closely related genes for functional human neutrophil IL-8 receptors have been cloned(12Cerretti D.P. Nelson N. Kozlosky C.J. Morrissey P.J. Copeland N.G. Gilbert D.J. Jenkins N.A. Dosik J.K. Mock B.A. Genomics. 1993; 18: 410-413Crossref PubMed Scopus (53) Google Scholar, 13Suzuki H. Prado G.N. Wilkinson N. Navarro J. J. Biol. Chem. 1994; 269: 18263-18266Abstract Full Text PDF PubMed Google Scholar, 14Cacalano G. Lee J. Kikly K. Ryan A.M. Pitts-Meek S. Hultgren B. Wood W.I. Moore M.W. Science. 1994; 265: 682-684Crossref PubMed Scopus (565) Google Scholar, 15Holmes W.E. Lee J. Kuang W.-J. Rice G.C. Wood W.I. Science. 1991; 253: 1278-1280Crossref PubMed Scopus (915) Google Scholar, 16Murphy P.M. Tiffany H.L. Science. 1991; 253: 1280-1283Crossref PubMed Scopus (763) Google Scholar, 17Ahuja S.K. Oczelik T. Milatovitch A. Francke U. Murphy P.M. Nature Genet. 1992; 2: 31-36Crossref PubMed Scopus (102) Google Scholar, 18Bozic C.R. Gerard N.P. von Uexkull-Guldenband C. Kolakowski Jr., L.F. Conklyn M.J. Breslow R. Showell H.J. Gerard C. J. Biol. Chem. 1994; 269: 29355-29358Abstract Full Text PDF PubMed Google Scholar). Mice lacking the IL-8 receptor homologue, created by gene knockout technology, exhibit expansion of neutrophils and B lymphocytes in the blood, bone marrow and lymphoid organs, and mobilize neutrophils poorly to sites of chemical irritation, suggesting a role for this receptor in both leukocyte differentiation and chemotaxis(14Cacalano G. Lee J. Kikly K. Ryan A.M. Pitts-Meek S. Hultgren B. Wood W.I. Moore M.W. Science. 1994; 265: 682-684Crossref PubMed Scopus (565) Google Scholar). The encoded receptor does not bind human IL-8, but instead binds the related α chemokines mouse KC and human MGSA (melanoma growth-stimulatory activity)(18Bozic C.R. Gerard N.P. von Uexkull-Guldenband C. Kolakowski Jr., L.F. Conklyn M.J. Breslow R. Showell H.J. Gerard C. J. Biol. Chem. 1994; 269: 29355-29358Abstract Full Text PDF PubMed Google Scholar). In contrast, cDNAs have been cloned for both human and mouse forms of the β chemokines MIP-1α, MIP-1β, RANTES, and MCP-1 (see (11Michiel D. Bio/Technology. 1993; 11: 739Crossref PubMed Scopus (5) Google Scholar) for alignment of the amino acid sequences and for primary references). cDNAs for three human leukocyte β chemokine-selective receptors have been cloned, one that is selective for MIP-1α and RANTES and two others that are selective for MCP-1(19Gao J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar, 20Neote K. DiGregorio D. Mak J.Y. Horuk R. Schall T.J. Cell. 1993; 72: 415-425Abstract Full Text PDF PubMed Scopus (699) Google Scholar, 21Charo I.F. Myers S.J. Herman A. Franci C. Connolly A.J. Coughlin S.R. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 2752-2756Crossref PubMed Scopus (650) Google Scholar). They are members of the rhodopsin-like superfamily of heptahelical, receptors and exhibit amino acid to each other and to the IL-8 J. Biol. 1992; 11: PubMed Scopus Google Scholar, P.M. Immunol. 1994; PubMed Scopus Google Scholar). of human leukocytes with of by binding and functional has that genes for receptor for MIP-1α, RANTES, and MCP-1 may but has been M. Dahinden C.A. Immunol. Today. 1994; 15: 127-133Abstract Full Text PDF PubMed Scopus (518) Google Scholar, 5Taub D.D. Conlon K. Lloyd A.R. Oppenheim J.J. Kelvin D.J. Science. 1993; 260: 355-358Crossref PubMed Scopus (705) Google Scholar, Sherry B. M.J. Kelvin D.J. Oppenheim J.J. J. Immunol. 1993; Google Scholar, Oppenheim J.J. Kelvin D.J. J. Exp. Med. 1993; 177: PubMed Scopus Google Scholar, G. S. R. Springer H. J. Exp. Med. 1993; 177: PubMed Scopus Google Scholar). have identified mouse leukocyte binding sites for MIP-1α and H. M. Broxmeyer H.E. Kwon B.S. J. Immunol. 1991; Google Scholar, G.J. M. Pragnell I.B. 1993; Google Scholar, H. R. Cell. Biol. 1993; PubMed Scopus Google Scholar). the RNA and of the first mouse β chemokine receptor the MIP-1α receptor In have two related genes for receptors whose and were from was from was from chain reaction were from human MIP-1α, MIP-1β, RANTES, and MCP-1 were from human chemokines were from for mouse MIP-1α and MIP-1β and human MIP-1α, which were from and human and and mouse which were from M. J. G. and M. respectively. In all chemokines used and were shown to of human leukocytes of a mouse in the were with a human MIP-1α/RANTES receptor with J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar). that to the in for were and the were with of the of and that to the were by and The sequences were on both The were from the by the for for and for and the for for and for all of the and the sites in the of and and in the of In to the the of and The reaction was of as a The were for by of for for and for with a for The were with by the system and were by from of the three cloned the and sites of the The of the cloned expression was by of an expression in for the human MIP-1α/RANTES receptor has been J.-L. Murphy P.M. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). K562 human cells were in K562 cells in were in the presence of of with a cells were in with B and for cells were in with B. of RNA was by for each cell RNA for the human MIP-1α/RANTES receptor binding of MIP-1α, MIP-1β, or RANTES were in K562 cells were in with human chemokines and of were in a of of with 1 and for 2 the cells were a and were The data were with the P.J. D. PubMed Scopus Google Scholar) to the and of binding leukocytes were by from by of were in The cells were 2 They were in and were were in with and with for in the The cells were with and 2 of the cell were in a in a was and and the data as the of and were leukocytes from the of were in RNA was by with and by in RNA was by on a and to a as J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar). of RNA from a of from a mouse was from were to to a with a and protein sequences were and the from the of J. Scopus Google Scholar) on a by the We the and gene for the human MIP-1α/RANTES receptor and other members of the seven-transmembrane-domain receptor the on a single J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar). to mouse an mouse with a human receptor were that to three distinct based on common patterns and and were for and and were and was in and to the human MIP-1α/RANTES receptor and to on and the functional have the MIP-1α receptor MIP-1α receptor-like 1 and MIP-1α receptor-like 2 The deduced sequences of MIP-1αR and the human MIP-1α/RANTES receptor are both amino in and sequences are 1 and respectively. of the mouse sequences has sites for whereas the human receptor has one in the The deduced protein of MIP-1αR is less from that of the human MIP-1α/RANTES receptor than In contrast, the sequences of and are less the protein and 63% than the and to the human MIP-1α/RANTES receptor, a in the of are chemokine MIP-1αR, MIP-1αRL1, and were stably in K562 and calcium mobilization was of known leukocyte chemokine to a of a protein and used to receptor in K562 cells and to mouse MIP-1α, mouse MIP-1β, or mouse or to any of the human MIP-1α, MIP-1β, RANTES, IL-8, and all tested and data not In contrast, human MIP-1α and mouse MIP-1α both of in MIP-1αR with an and and RANTES was a less potent agonist than MIP-1α, a for calcium mobilization > of the other chemokines including mouse MIP-1β, were agonists for calcium mobilization by MIP-1αR. activation, most receptors have to with the activating agonist and other known as has been for the human MIP-1α/RANTES receptor and a β chemokine receptor encoded by of human K. DiGregorio D. Mak J.Y. Horuk R. Schall T.J. Cell. 1993; 72: 415-425Abstract Full Text PDF PubMed Scopus (699) Google Scholar, J.-L. Murphy P.M. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). MIP-1αR were MIP-1α of the cells to with the In contrast, RANTES, MIP-1β, or MCP-1 no on the to with MIP-1α the high selectivity of MIP-1αR for the functional of MIP-1αR to leukocytes were from the of for the MIP-1αR human MIP-1α a calcium in mouse leukocytes whereas human RANTES was less potent The patterns for MIP-1αR and mouse leukocytes were also with MIP-1α, mouse leukocytes were to but to the agonist N-formyl-methionyl-leucyl-phenylalanine In contrast, with RANTES no on the to the of the calcium by human MIP-1α were for both K562 cells and mouse leukocytes, is important to that the were respectively. to the for this the ability of MIP-1αR, MIP-1αRL1, and to with binding was K562 cells and specifically bound MIP-1α, MIP-1β, or RANTES and data not MIP-1αR were to specifically bind 125I-human MIP-1α and 125I-human RANTES and of competition binding with 125I-human MIP-1α as the a single of binding with of and for human MIP-1α and mouse MIP-1α, B and human MIP-1α from a was an of was is the of the human MIP-1α protein that was and the human MIP-1α used in binding of β chemokines to the mouse MIP-1α receptor. K562 cells stably transfected with MIP-1αR were with MIP-1α or RANTES and binding was in the presence of of the chemokines identified in the the of each RANTES, and IL-8 were human binding was and The of binding sites cell P.J. D. PubMed Scopus Google Scholar) for 125I-human MIP-1α and human MIP-1α data was The shown are from a single of two with both and all binding of 125I-human MCP-1 not in In with K562 cells stably transfected with and binding not with any of the four β of 125I-human MIP-1α and 125I-human RANTES by MIP-1αR by all β chemokines but not by the α chemokine IL-8 The rank order and of competition on the of the For 125I-human MIP-1α, the rank order was human MIP-1α > mouse MIP-1α∼ RANTES ∼ MIP-1β > for 125I-human RANTES, the rank order was human MIP-1α∼ RANTES > MIP-1β > MCP-1. The of competition by MIP-1β and MCP-1 was for the than the whereas the of competition by MIP-1α was the for both The of competition by RANTES was less than MIP-1α for both the and with RANTES competition binding have been for the human MIP-1α/RANTES receptor in human K. DiGregorio D. Mak J.Y. Horuk R. Schall T.J. Cell. 1993; 72: 415-425Abstract Full Text PDF PubMed Scopus (699) Google Scholar). of of the for RANTES binding was not The of MCP-1 with MIP-1αR by the competition binding was by the of binding of to the MIP-1αR transfected cells of bound specifically to the MIP-1αR Graham G.J. M. Pragnell I.B. 1993; Google Scholar) have that K562 cells specifically bind MIP-1α and that binding by β but not by α They not binding We RANTES, and MCP-1 binding to K562 cells but the were to binding to MIP-1αR and human MIP-1α/RANTES receptor and not K562 cells binding sites for MIP-1α, RANTES, and MCP-1 > and to exhibit a calcium by chemokines > were to RNA for the human MIP-1α/RANTES receptor in K562 cells by We have also shown that human cell or stably transfected with MIP-1αR or the human MIP-1α/RANTES receptor, exhibit calcium to β chemokines that are with the K562 and M. 2 the data that the binding and calcium in the MIP-1αR transfected cells are by the cloned mouse gene The of β chemokine binding to K562 cells to the cloned β chemokine receptors the of MIP-1αR, MIP-1αRL1, and the were used to identical of RNA from mouse leukocytes and of RNA from mouse solid high The not and not to other mouse genes all three genes were in mouse leukocytes, each a unique expression in solid For MIP-1αR, three were identified in mouse leukocyte The was whereas the two were and The but not the was also detected in heart, spleen, and is important to that the is and a of that differ in For MIP-1αRL1, two were identified in mouse leukocyte RNA that were and The identified a single in skeletal no other solid were For MIP-1αRL2, three were detected in mouse leukocyte The two were and whereas the was three of were also detected in spleen and with the but not in other solid of the In the have the amino acid RNA high and of the first mouse β chemokine receptor, MIP-1αR. In addition, have two related genes for chemokine receptors whose and human three genes have been to mouse in a of conserved with the gene for the human MIP-1α/RANTES receptor. J.-L. and M. for of the leukocyte chemokine receptors cloned so far bind either α or β but not to chemokines from both and to calcium-mobilizing D.P. Nelson N. Kozlosky C.J. Morrissey P.J. Copeland N.G. Gilbert D.J. Jenkins N.A. Dosik J.K. Mock B.A. Genomics. 1993; 18: 410-413Crossref PubMed Scopus (53) Google Scholar, 13Suzuki H. Prado G.N. Wilkinson N. Navarro J. J. Biol. Chem. 1994; 269: 18263-18266Abstract Full Text PDF PubMed Google Scholar, 15Holmes W.E. Lee J. Kuang W.-J. Rice G.C. Wood W.I. Science. 1991; 253: 1278-1280Crossref PubMed Scopus (915) Google Scholar, 16Murphy P.M. Tiffany H.L. Science. 1991; 253: 1280-1283Crossref PubMed Scopus (763) Google Scholar, 18Bozic C.R. Gerard N.P. von Uexkull-Guldenband C. Kolakowski Jr., L.F. Conklyn M.J. Breslow R. Showell H.J. Gerard C. J. Biol. Chem. 1994; 269: 29355-29358Abstract Full Text PDF PubMed Google Scholar, J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar, 20Neote K. DiGregorio D. Mak J.Y. Horuk R. Schall T.J. Cell. 1993; 72: 415-425Abstract Full Text PDF PubMed Scopus (699) Google Scholar, 21Charo I.F. Myers S.J. Herman A. Franci C. Connolly A.J. Coughlin S.R. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 2752-2756Crossref PubMed Scopus (650) Google Scholar, J. Biol. 1992; 11: PubMed Scopus Google Scholar). The β chemokines MIP-1α and RANTES bind to MIP-1αR with the affinity. and human forms of MIP-1α were whereas human RANTES was a agonist for MIP-1αR. We the mouse receptor MIP-1αR to the high of MIP-1α to human RANTES and the other chemokines The human MIP-1α/RANTES receptor is also selective for MIP-1α than for RANTES, calcium mobilization is in with receptor or in transfected and K562 but the differ only by less than for J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar, 20Neote K. DiGregorio D. Mak J.Y. Horuk R. Schall T.J. Cell. 1993; 72: 415-425Abstract Full Text PDF PubMed Scopus (699) Google Scholar, J.-L. Murphy P.M. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). human and mouse RANTES are identical in amino acid T.J. Mak J.Y. J. Immunol. 1992; 22: PubMed Scopus Google is that mouse RANTES also activate MIP-1αR, with than human RANTES. mouse RANTES has not been tested in functional from cells mouse RANTES have been shown to chemoattractant for human monocytes in T.J. Mak J.Y. J. Immunol. 1992; 22: PubMed Scopus Google Scholar). mouse RANTES two than human RANTES, MIP-1αR than the human MIP-1α/RANTES receptor in the to for These in for RANTES the between chemokine and receptor for high binding and high calcium but MIP-1α and RANTES for binding to MIP-1αR, and respectively. of this is the β chemokine receptor encoded by of human which have J.-L. Murphy P.M. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). MIP-1α, RANTES, MIP-1β, and MCP-1 are with 125I-human MIP-1α for binding to the in transfected K562 RANTES is a potent agonist than the other three calcium mobilization is The and functional of the and β chemokine receptors may for that are for the selectivity of receptors to β The of RANTES binding to MIP-1αR shown by competition with either RANTES or MIP-1α, whereas for the human MIP-1α/RANTES receptor, of RANTES has been to an in the K. DiGregorio D. Mak J.Y. Horuk R. Schall T.J. Cell. 1993; 72: 415-425Abstract Full Text PDF PubMed Scopus (699) Google Scholar). In were also with the RANTES binding in that the of competition RANTES was than that with MIP-1α binding of MIP-1αR with MIP-1β and MCP-1 were from competition binding and shown for However, were to identify any functional in the form of agonist or for by calcium In this both human and mouse forms of MIP-1β were that MIP-1β and MCP-1 bind to the receptor and activate a not The rank order of of MIP-1α and RANTES for calcium mobilization by mouse leukocytes and by MIP-1αR in transfected K562 and the of MIP-1αR RNA in leukocytes, that MIP-1αR the mouse leukocyte calcium to of leukocyte and to the functional of this receptor. H. M. Broxmeyer H.E. Kwon B.S. J. Immunol. 1991; Google Scholar) have identified of high binding sites for mouse MIP-1α on mouse lymphocytes and the mouse macrophage cell and but the of other chemokines to binding sites is We were to MIP-1αR in RNA by cells to MIP-1α calcium mobilization was not Graham G.J. M. Pragnell I.B. 1993; Google Scholar) have binding sites for MIP-1α on the mouse hematopoietic stem cell that may shared with other β but not α with MIP-1α has and variable on the cell MIP-1αR is for of cells is were to the shared by and with MIP-1αR and expression in that are β the have been in the that tested the receptor to or to to the of stably transfected the receptors not to calcium-mobilizing in K562 the is one of that was not used in binding to transfected or the receptors bind only the mouse form of a human that receptors bind β or less a The of which is to and to bind has a of and the whereas other chemokine including the human MIP-1α/RANTES receptor, MIP-1αR and MIP-1αRL2, are in this and have the The of between and is whereas the sequences for the MIP-1α/RANTES receptor, MIP-1αR, and are all is that are The of for MIP-1αR, MIP-1αRL1, and in solid that the targets for β chemokine action may than has been The expression of is RNA is in skeletal the solid organs, and only in in The differential RNA expression patterns shown in 7 tissue-specific for the encoded The data not the cell for the RNA the three genes are all in leukocytes but have unique expression patterns in solid organs, is that the in solid from leukocytes the RNA for the human MIP-1α/RANTES receptor is in neutrophils, eosinophils, and lymphocytes of human blood, and in human B J.-L. Kuhns D.B. Tiffany H.L. McDermott D. Li X. Francke U. Murphy P.M. J. Exp. Med. 1993; 177: 1421-1427Crossref PubMed Scopus (339) Google Scholar, C. S.K. Murphy P.M. Biol. Google and U. that the for MIP-1αR in mouse leukocyte RNA are the of from RNA in the mouse leukocyte The of for MIP-1αR, MIP-1αRL1, and were all that only the the and are to the that are either from in the or from to the of distinct The by the three on the that the genes MIP-1αR, MIP-1αRL1, or Furthermore, high of the three to mouse to identify any other The most for the RNA is of in the differential of in the In the human IL-8 receptor genes and the human MIP-1α/RANTES receptor gene all to distinct in S.K. A. Tiffany H.L. Murphy P.M. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google The for MIP-1αR, MIP-1αRL1, and is to the of to MIP-1αR a new for the by which MIP-1α leukocyte and in the mouse. also this receptor the of MIP-1α on MIP-1αR is structurally and to the human MIP-1α/RANTES receptor, both receptors are to a role in the of and and tissue-specific expression patterns new targets for the of β chemokines in the mouse. human chemokine receptor selective for MIP-1α, RANTES, and MIP-1β has been deduced is most to mouse C. S.K. Murphy P.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). We H. Tiffany for