Cloning and characterization of a novel murine macrophage inflammatory protein-1 alpha receptor.
We have cloned a novel CC chemokine receptor cDNA from mouse thymus. The deduced amino acid sequence shows 74% identity to the human monocyte chemotactic protein (MCP)-1 receptor (CC CKR-2b) and 54% to a recently cloned murine macrophage inflammatory protein (MIP)-1alpha receptor (Gao, J. L., and Murphy, P. M.(1995) J. Biol. Chem. 270, 17494-17501). Northern blot analysis of mouse tissues showed that the mRNA was also expressed in heart, spleen and liver, and to a lesser extent in lung and brain. The rank order of CC chemokine competition for 125I-labeled human RANTES (regulated on activation, normal T-cell expressed and secreted) binding to human embryonic kidney (HEK) 293 cells stably transfected with the receptor cDNA was murine MIP-1alpha >> human MIP-1beta > human RANTES > murine RANTES > murine MIP-1beta > human MCP-2 > murine MCP-1 (JE) > human MIP-1alpha > human MCP-3 > human MCP-1. Of the chemokines tested, only murine MIP-1alpha, human and murine MIP-1beta and RANTES, human MCP-2, and JE were able to induce mobilization of intracellular Ca2+ from fura-2-loaded HEK 293 cells expressing the receptor. These results suggest that this receptor functions as a high affinity murine MIP-1alpha receptor; however, it is likely to be an important target for the biological activities of several CC chemokines in mouse.
Meyer
A
A
Glaxo Institute for Molecular Biology, CH-1228, Plan-les-Ouates, Geneva, Switzerland.
Coyle
A J
AJ
Proudfoot
A E
AE
Wells
T N
TN
Power
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D018932:Chemokine CCL2 / Q000737:chemistry / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008969:Molecular Sequence Data; D015846:Monokines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000737:chemistry*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013950:Thymus Gland / Q000276:immunology*; D014158:Transcription, Genetic; D014162:Transfection
C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D018076:DNA, Complementary; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; C080633:macrophage inflammatory protein 1alpha receptor; D002118:Calcium