KiSS-1 receptor (KISS1R) is a ~42 kDa protein. Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54). The hypothalamic KISS1/KISS1R signaling system plays a central role in the regulation of the hypothalamic-pituitary-gonadal reproductive axis by modulating the secretion of gonadotropin-releasing hormone (GnRH) from GnRH neurons. In these neurons, kisspeptin binding to its receptor activates G(q)-dependent signaling, leading to phospholipase C (PLC) activation, and hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). The subsequent rise in intracellular calcium levels results in the inhibition of inward rectifier potassium channels and activation of TRPC-like cation channels, leading to GnRH neurons depolarization and stimulation. In addition to this pathway, kisspeptin also triggers G(q)-independent signaling via beta-arrestin, leading to MAPK cascade activation and ERK1/ERK2 phosphorylation. 1. Kotani, M. et al. (2001) The Journal of biological chemistry 276, 34631-6. PMID: 114578432. Hori, A. et al. (2001) Biochemical and biophysical research communications 286, 958-63. PMID: 115273933. Bilban, M. et al. (2004) Journal of cell science 117, 1319-28. PMID: 150206724. Becker, JA. et al. (2005) Biochemical and biophysical research communications 326, 677-86. PMID: 155961535. de Roux, N. et al. (2003) Proceedings of the National Academy of Sciences of the United States of America 100, 10972-6. PMID: 129445656. Seminara, SB. et al. (2003) The New England journal of medicine 349, 1614-27. PMID: 145737337. Semple, RK. et al. (2005) The Journal of clinical endocrinology and metabolism 90, 1849-55. PMID: 155986878. Tenenbaum-Rakover, Y. et al. (2007) The Journal of clinical endocrinology and metabolism 92, 1137-44. PMID: 171643109. Teles, MG. et al. (2008) The New England journal of medicine 358, 709-15. PMID: 18272894 | 
