Metastasis-suppressor KiSS-1 (KISS1) is a ~14 kDa protein. Kisspeptins are ligands for the G-protein coupled receptor KISS1R/GPR54. 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. 2. Kotani, M. et al. (2001) The Journal of biological chemistry 276, 34631-6. PMID: 114578433. Hori, A. et al. (2001) Biochemical and biophysical research communications 286, 958-63. PMID: 115273935. Bilban, M. et al. (2004) Journal of cell science 117, 1319-28. PMID: 150206726. Becker, JA. et al. (2005) Biochemical and biophysical research communications 326, 677-86. PMID: 155961537. Matsui, H. et al. (2004) Biochemical and biophysical research communications 320, 383-8. PMID: 152198398. Semple, RK. et al. (2005) The Journal of clinical endocrinology and metabolism 90, 1849-55. PMID: 155986879. Topaloglu, AK. et al. (2012) The New England journal of medicine 366, 629-35. PMID: 22335740 | 
