Activation of MAPK cascades by G-protein-coupled receptors: The case of gonadotropin-releasing hormone receptor

G-protein-coupled receptors (GPCRs) are a large group of integral membrane receptors that transmit signals from a diverse array of external stimuli, i ncluding neurotransmitters, hormones, phospholipids, photons, odorants and taste ligands. In response to ligand binding, the GPCRs initiate diverse do wnstream signaling pathways through four groups of G proteins and other int eracting proteins. Key, components in GPCR-induced intracellular signaling are four groups of mitogen-activated protein kinase (MAPK) cascades: extrac ellular signal-related kinase (ERK), Jun N-terminal kinase (JNK), p38MAPK a nd big MAPK (BMK). The hallmark of MAPK signaling is the stimulation-depend ent nuclear translocation of the involved kinases, which regulate gene expr ession and the cytoplasmic acute response to mitogenic, stress-related, apo ptotic and survival stimuli. A special type of GPCR is the gonadetropin-rel easing hormone (GnRH) receptor which uses primarily the Gq protein for its downstream signaling. GnRH activates all four MAPK cascades by a PKC-depend ent mechanism. Common signaling molecules, including the tyrosine kinase c- SRC and the small GTPases CDC42, RAC and RAS, are implicated in various asp ects of the GnRH-MAPK pathways. Thus, the activation of MAPK cascades by Gn RH opens a new vista in the understanding of the transcriptional regulation of genes encoding gonadotropins. However, additional studies on cell lines and whole animals ai-e required to understand GnRH signaling in the contex t of other hormones during the reproductive cycle of mouse and human.