Journal of Biological Chemistry2001Open AccessHighly Cited

The Metastasis Suppressor Gene KiSS-1 Encodes Kisspeptins, the Natural Ligands of the Orphan G Protein-coupled Receptor GPR54

Masato Kotani, Michel Detheux, Ann L. Vandenbogaerde et al.

1,529 citations2001Open Access — see publisher for license terms1 related compound

Research Article — Peer-Reviewed Source

Original research published by Kotani et al. in Journal of Biological Chemistry. Redistributed under Open Access — see publisher for license terms. MedTech Research Group provides these references for informational purposes. We do not conduct original research. All studies are the work of their respective authors and institutions.

Abstract

Natural peptides displaying agonist activity on the orphan G protein-coupled receptor GPR54 were isolated from human placenta. These 54-, 14,- and 13-amino acid peptides, with a common RF-amide C terminus, derive from the product of KiSS-1, a metastasis suppressor gene for melanoma cells, and were therefore designated kisspeptins. They bound with low nanomolar affinities to rat and human GPR54 expressed in Chinese hamster ovary K1 cells and stimulated PIP<sub>2</sub> hydrolysis, Ca<sup>2+</sup> mobilization, arachidonic acid release, ERK1/2 and p38 MAP kinase phosphorylation, and stress fiber formation but inhibited cell proliferation. Human GPR54 was highly expressed in placenta, pituitary, pancreas, and spinal cord, suggesting a role in the regulation of endocrine function. Stimulation of oxytocin secretion after kisspeptin administration to rats confirmed this hypothesis.

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Article Details
DOI10.1074/jbc.m104847200
JournalJournal of Biological Chemistry
Year2001
AuthorsMasato Kotani, Michel Detheux, Ann L. Vandenbogaerde, David Communi, Jean‐Marie Vanderwinden, Emmanuel Le Poul, Stéphane Brézillon, Richard Tyldesley, Nathalie Suarez-Huerta, Fabrice Vandeput, Cédric Blanpain, Serge N. Schiffmann, Gilbert Vassart, Marc Parmentier
LicenseOpen Access — see publisher for license terms
Citations1,529