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Originally published In Press as doi:10.1074/jbc.M102743200 on May 31, 2001

J. Biol. Chem., Vol. 276, Issue 31, 28969-28975, August 3, 2001
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AXOR12, a Novel Human G Protein-coupled Receptor, Activated by the Peptide KiSS-1*

Alison I. Muira, Larissa Chamberlainb, Nabil A. Elshourbagyc, David Michalovichde, Darren J. Mooreb, Amy Calamaric, Philip G. Szekeresa, Henry M. Sarauf, Jon K. Chambersa, Paul Murdockg, Klaudia Steplewskic, Usman Shabonc, Jane E. Millera, Susan E. Middletona, John G. Darkerh, Christopher G. C. Larminied, Shelagh Wilsona, Derk J. Bergsmac, Piers Emsonb, Richard Faulli, Karen L. Philpottj, and David C. Harrisonjk

From the Departments of j Neurology, a Discovery Biology, g Biotechnology and Genetics, h Discovery Chemistry, and d Bioinformatics, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom, the Departments of c Biotechnology and Genetics and f Pulmonary Biology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania, 19406, the b Neurobiology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom, and the i Department of Anatomy with Radiology, University of Auckland, P. O. Box 92019, Auckland, New Zealand

A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homology to the rat orphan receptor GPR54, was cloned from a human brain cDNA library. Heterologous expression of AXOR12 in mammalian cells permitted the identification of three surrogate agonist peptides, all with a common C-terminal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of which prevents metastasis in melanoma cells. Quantitative reverse transcriptase-polymerase chain reaction was used to study the expression of AXOR12 and KiSS-1 in a variety of tissues. The highest levels of expression of AXOR12 mRNA were observed in brain, pituitary gland, and placenta. The highest levels of KiSS-1 gene expression were observed in placenta and brain. A polyclonal antibody raised to the C terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression patterns and the nature of the putative cognate ligand for AXOR12 are discussed.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AJ309020.

e Current Address: Inpharmatica Ltd., 60 Charlotte St., London W1T 2NU, United Kingdom.

k To whom correspondence should be addressed. Tel.: 44-0-1279-622728; Fax: 44-0-1279-622371; E-mail: David_C_Harrison@gsk.com.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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