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Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE<jats:sub>2<\/jats:sub>and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.<\/jats:p>","DOI":"10.1139\/y05-127","type":"journal-article","created":{"date-parts":[[2006,8,3]],"date-time":"2006-08-03T00:21:13Z","timestamp":1154564473000},"page":"287-297","source":"Crossref","is-referenced-by-count":146,"title":["G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigmThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell."],"prefix":"10.1139","volume":"84","author":[{"given":"Fernand","family":"Gobeil","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universit\u00e9 de Sherbrooke, 3001, 12th North Avenue, Fleurimont, QC J1H 5N4, Canada."},{"name":"Department of Pediatric, Ophthalmology and Pharmacology, Research Centre of H\u00f4pital Sainte-Justine, 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