Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor.
A DNA fragment encoding an amino acid sequence possessing common features to the G protein-coupled receptor (GPCR) superfamily was found in the human genomic sequence, and from this information, the full-length cDNA of a novel GPCR, designated SLT, was cloned from the human hippocampus cDNA library. SLT showed the highest homology to the melanin-concentrating hormone (MCH) receptor, SLC-1 (31.5% identity), and to a lesser extent, to the somatostatin (SST) receptor subtypes. MCH exhibited agonistic behavior when applied to the SLT-expressing CHO cells at subnanomolar doses whereas more than 200 known peptides, including SST and cortistatin, did not. These results indicated that MCH is the cognate ligand of the SLT receptor and that this newly cloned GPCR is the second subtype of the MCH receptor. Quantitative polymerase chain reaction analysis of the SLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues. The distribution of the SLT nearly overlapped that of SLC-1, suggesting that some of the neural functions of MCH may be mediated by both of these receptor subtypes.
Mori
M
M
Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki, 300-4293, Japan. Mori_Masaaski@takeda.co.jp
Harada
M
M
Terao
Y
Y
Sugo
T
T
Watanabe
T
T
Shimomura
Y
Y
Abe
M
M
Shintani
Y
Y
Onda
H
H
Nishimura
O
O
Fujino
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015723:Gene Library; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D017931:DNA Primers; C103263:MCHR1 protein, human; C491208:MCHR1 protein, rat; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; C092274:melanin-concentrating hormone receptor; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins