Molecular cloning of a novel human melanocortin receptor.
A human genomic clone designated MC-2 is isolated. The cloned DNA codes for a protein of 325 amino acids which possesses seven hydrophobic segments, a characteristic of G-protein coupled receptors. The MC-2 receptor is expressed in brain tissue but not in the melanoma cells. When the MC-2 DNA is expressed in COS-7 cells, it binds [125I]-labelled [Nle4, D-Phe7]- alpha melanocyte stimulating hormone (NDP-MSH) which then could be displaced by melanotropic peptides alpha-MSH, beta-MSH, gamma-MSH and adrenocorticotropic hormone, but not by non-melanotropic peptide beta-endorphin. The highest affinity of 5.18 nM was for the NDP-MSH peptide. The novel MC-2 receptor and the MC-1 receptor, described earlier by us (8) showed identical order of affinity for the melanocortin peptides, but the affinities and the fold differences in the affinities to the melanocortin peptides were different when compared to the earlier described MC-1 receptor. The results suggest that the MC-2 DNA codes for a novel melanocortin receptor.
Department of Pharmaceutical Pharmacology, Biomedical Centre, Uppsala, Sweden.
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Chhajlani
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Muceniece
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Wikberg
D000595:Amino Acid Sequence; D001483:Base Sequence; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D004247:DNA / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007700:Kinetics; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D044103:Receptor, Melanocortin, Type 2; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D009074:Melanocyte-Stimulating Hormones; D004247:DNA; D019204:GTP-Binding Proteins