KiSS1-derived peptide receptor
| KISS1R | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 19: 0.92 – 0.92 Mb | Chr 10: 79.75 – 79.76 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
The KiSS1-derived peptide receptor (also known as GPR54 or the Kisspeptin receptor) is a
KISS1, which is expressed in a variety of endocrine and gonadal tissues.[9] Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.[10]
mediobasal hypothalamus (MBH) project to GnRH neurons in the median eminence, which expresses KISS1R, to stimulate LH secretions in a pulsatile manner from the anterior pituitary to initiate ovulation/ pubertal maturation.[14][15][16] The KISS1 and KISS1R/GPR54 genes have been detected in the brain, pituitary, placenta, pancreas, liver, and small intestine.[14]
Function
Kisspeptin is involved in the regulation of endocrine function and the onset of
oestradiol but enhanced by GnRH.[19] Reductions in kisspeptin levels with age may conversely be one of the reasons behind age-related declines in levels of other endocrine hormones such as luteinizing hormone.[20]
Clinical significance
Alterations in the KISS1/KISS1R signaling pathway have been linked to multiple physiological conditions, including metabolic and reproductive abnormalities.[21] A knockout model of GPR54/KISS1R in mice showed hypogonadism, and the mice failed to reach puberty.[21] The KISS1 gene has been stated to suppress the metastasis of malignant melanomas.[22] KISS1R signaling pathway has been characterized in the suppression of tumors and has anti-metastatic effects in several cancers, including breast cancer.[23][24]
Activation of KISS1R elicits a neuroendocrine response leading to pubertal maturation. This is indicated by intermittent kisspeptin-10 administration to pre-pubertal animals resulting in activation of the
hypothalamic-pituitary axis and subsequent precocious puberty in rats and primates.[25][26] Mutations in the kisspeptin receptor KISS1R have resulted in isolated hypogonadotropic hypogonadism (IHH), characterized by delayed or absence of puberty [27]
Ligands
No non-peptide ligands for this receptor have yet been discovered, but as of 2009 both selective agonist and antagonist peptides are known.
Agonists
- Kisspeptin (kisspeptin-54, metastin)
- Kisspeptin-10 (112-121 C-terminal fragment)[28]
- KISS1-305
- MVT-602 (RVT-602, TAK-448)
- TAK-683
Antagonists
- Kisspeptin-10 analogues modified with amino substitutions[29]
- Kisspeptin-234
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000116014 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035773 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 38910830.
- S2CID 205017670.
- PMID 11387329.
- PMID 11457843.
- S2CID 22875820.
- PMID 18483150.
- PMID 19109311.
- PMID 24937427.
- PMID 24703698.
- ^ PMID 29755406.
- S2CID 14817781.
- S2CID 3542864.
- PMID 15684075.
- PMID 16282350.
- S2CID 205345039.
- PMID 19423763.
- ^ PMID 14652023.
- PMID 18219339.
- PMID 24155777.
- S2CID 210883188.
- PMID 15486019.
- PMID 16282350.
- PMID 20237166.
- S2CID 6587724.
- PMID 19321788.
Further reading
- Colledge WH (November 2004). "GPR54 and puberty". Trends in Endocrinology and Metabolism. 15 (9): 448–453. S2CID 44517221.
- Kaiser UB, Kuohung W (April 2005). "KiSS-1 and GPR54 as new players in gonadotropin regulation and puberty". Endocrine. 26 (3): 277–284. S2CID 22795399.
- Seminara SB (2006). "Metastin and its G protein-coupled receptor, GPR54: critical pathway modulating GnRH secretion". Frontiers in Neuroendocrinology. 26 (3–4): 131–138. S2CID 40864875.
- Tena-Sempere M (2006). "GPR54 and kisspeptin in reproduction". Human Reproduction Update. 12 (5): 631–639. PMID 16731583.
- Cerrato F, Seminara SB (March 2007). "Human genetics of GPR54". Reviews in Endocrine & Metabolic Disorders. 8 (1): 47–55. S2CID 13041509.
- Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, et al. (March 1999). "Discovery of a receptor related to the galanin receptors". FEBS Letters. 446 (1): 103–107. S2CID 38910830.
- Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, et al. (May 2001). "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor". Nature. 411 (6837): 613–617. S2CID 205017670.
- Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, et al. (August 2001). "AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1". The Journal of Biological Chemistry. 276 (31): 28969–28975. PMID 11387329.
- Clements MK, McDonald TP, Wang R, Xie G, O'Dowd BF, George SR, et al. (June 2001). "FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54". Biochemical and Biophysical Research Communications. 284 (5): 1189–1193. PMID 11414709.
- Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. (September 2001). "The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54". The Journal of Biological Chemistry. 276 (37): 34631–34636. PMID 11457843.
- Hori A, Honda S, Asada M, Ohtaki T, Oda K, Watanabe T, et al. (September 2001). "Metastin suppresses the motility and growth of CHO cells transfected with its receptor". Biochemical and Biophysical Research Communications. 286 (5): 958–963. PMID 11527393.
- Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD, Saji M (May 2002). "Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells". The Journal of Clinical Endocrinology and Metabolism. 87 (5): 2399. PMID 11994395.
- Janneau JL, Maldonado-Estrada J, Tachdjian G, Miran I, Motté N, Saulnier P, et al. (November 2002). "Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells". The Journal of Clinical Endocrinology and Metabolism. 87 (11): 5336–5339. PMID 12414911.
- Bo-Abbas Y, Acierno JS, Shagoury JK, Crowley WF, Seminara SB (June 2003). "Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes". The Journal of Clinical Endocrinology and Metabolism. 88 (6): 2730–2737. PMID 12788881.
- Ikeguchi M, Hirooka Y, Kaibara N (September 2003). "Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in hepatocellular carcinoma". Journal of Cancer Research and Clinical Oncology. 129 (9): 531–535. S2CID 20323621.
- de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (September 2003). "Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54". Proceedings of the National Academy of Sciences of the United States of America. 100 (19): 10972–10976. PMID 12944565.
- Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al. (October 2003). "The GPR54 gene as a regulator of puberty". The New England Journal of Medicine. 349 (17): 1614–1627. PMID 14573733.
- Ikeguchi M, Yamaguchi K, Kaibara N (February 2004). "Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma". Clinical Cancer Research. 10 (4): 1379–1383. PMID 14977840.
- Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, et al. (March 2004). "Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts". Journal of Cell Science. 117 (Pt 8): 1319–1328. S2CID 38523546.
External links
- "KiSS1-Derived Peptide Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-02-06. Retrieved 2007-11-02.
- KISS1R+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.