KISS1R

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 (By similarity). In addition to this pathway, kisspeptin also triggers G(q)-independent signaling via beta-arrestin, leading to MAPK cascade activation and ERK1/ERK2 phosphorylation. Furthermore, activation of KISS1R by kisspeptin-10 recruits phosphatase DUSP18 and SRC to the KISS1R C-terminus through a G(q)-dependent signaling pathway, leading to DUSP18-mediated dephosphorylation of SRC. In bone tissue, this results in down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). KISS1R is also involved in the regulation of other processes, including cell proliferation and cell migration..

Function from UniProtKB (Q969F8), read 2026-09-23. CC BY 4.0.