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

By M. Kotani, M. Detheux, A. Vandenbogaerde, D. Communi, J. Vanderwinden, E. Le Poul, S. Brézillon, R. Tyldesley, Nathalie Suarez-Huerta, F. Vandeput and 4 more. Journal of Biological Chemistry, 2001

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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 PIP2 hydrolysis, Ca2+ 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.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Reproductive Medicine

View Paper: https://www.semanticscholar.org/paper/f9f49ffcbb058f563e23253997b3196282d3bfc9

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In Molecular Biology

1. D. Clifton
2. R. Steiner
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In Reproductive Medicine

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Citations in the corpus

• Neuroendocrinology of reproduction in teleost fish. (2010, background): “The kisspeptins are the products of the KiSS1 gene, which encodes for a 145 amino acid precursor protein that is cleaved to yield a family of four biologically active peptides, 54, 14, 13 and 10 amino acids long (Kotani et al., 2001).”
• Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids (2003, methodology): “A functional assay based on the luminescence of mitochondrial aequorin (12) was performed as previously described ( 13 ).”
• Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. (2005, background): “GPR54-deficient (GPR54 / ) mice have abnormal sexual development, have low circulating gonadotropin concentrations, and are infertile (5, 6).”
• Kisspeptins and reproduction: physiological roles and regulatory mechanisms. (2012, methodology): “Such an increase in phosphatidylinositol turnover has been demonstrated for both human and mouse GPR54 (228, 434).”
• Kisspeptin signaling in the brain. (2009, background): “cleaved into the shorter products (2).”
• Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. (2004, background): “This peptide is the rodent homologue of human KiSS-1112–121-NH2 or kisspeptin 10, which was previously shown to maximally bind and activate GPR54 in transfected Chinese hamster ovary cells (12, 13).”
• Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017, background): “Kisspeptin is a hypothalamic peptide encoded by the KiSS 1 gene (Kotani et al., 2001) and it has been found to be a potent stimulus for GnRH secretion (Herbison, 2016).”