Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gq-coupled receptors

International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

“…There is substantial evidence that the kisspeptin receptor couples to the G␣ q/11 signaling pathway, activating PLC, to result in phosphatidylinositol 4,5-bisphosphate hydrolysis followed by accumulation of inositol-(1,4,5)-triphosphate and diacylglycerol to cause subsequent Ca 2ϩ mobilization (Kotani et al, 2001;Muir et al, 2001;Ohtaki et al, 2001). Other signaling pathways activated seem to be cell type-dependent, and proposed downstream mediators include protein kinase C, arachidonic acid, mitogen activated protein kinases (such as extracellular signal-regulated kinase 1/2 and p38), and phosphatidylinositol-3-kinase/ Akt (Kotani et al, 2001;Muir et al, 2001;Ringel et al, 2002;Becker et al, 2005;Stathatos et al, 2005). Signaling through inositol-(1,4,5)-triphosphate is also consistent with the potential vasoconstrictor role of kisspeptin (see section VIII.C).…”

Kisspeptin-10-Induced Signaling of GPR54 Negatively Regulates Chemotactic Responses Mediated by CXCR4: a Potential Mechanism for the Metastasis Suppressor Activity of Kisspeptins

“…Depending on the cellular environment and the subtypes of signaling molecules involved, one or the other may prevail. However, very recently (33), new information showed that the signaling of the GPR54 in breast tumor cells could specifically promote the expression of an array of proapoptotic genes, suggesting that it may cross the line between metastasis suppressors and tumor suppressors.…”

Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas

“…Thus, kisspeptin-13 might block insulin release by interacting with GPR54 present in pancreatic B cells. GPR54 couples primarily with G aq/11 proteins, leading to PLC activation, phosphatidylinositol (PI) turnover, and increase in intracellular calcium and protein kinase C activity (Kotani et al 2001, Muir et al 2001, Ohtaki et al 2001, Stafford et al 2002, Becker et al 2005. Activation of this pathway in the B cell is associated with an increase in insulin secretion, as has been reported for activation of muscarinic receptors by carbachol (Zawalich 1996, Gilon & Henquin 2001, Flatt 2003, and thus it cannot explain the insulinostatic effect of kisspeptin-13 found in the present study.…”