title: Subcellular G-protein coupled receptor signaling hints at greater therapeutic selectivity.
abstract: G-protein coupled receptors (GPCRs) evolved as specialized sensors of the extracellular environment. Comprising the largest family of cell surface receptors, GPCRs are common therapeutic targets. Over the last 25 years, several GPCRs have been observed at the cell nucleus, suggesting the presence of intracrine GPCR signaling beyond the plasma membrane. Yet specific physiological functions of nuclear GPCRs had not been reported, until lately. We recently uncovered distinct but complementary angiogenic roles of F2rl1 (formerly known as PAR2) depending on its subcellular localization at the plasma membrane or at the nucleus. Targeting subcellular compartments to improve drug selectivity may therefore inspire novel therapeutic strategies for transmembrane receptors.
authors.affiliation: Université de Montréal, CHU Ste-Justine Hospital Research Centre, Departments of Pediatrics, Ophthalmology and Pharmacology , 3175 Côte Ste-Catherine, Montréal, Qc, H3T 1C5 , Canada +1 514 345 4931 Ext. 2978 ; +1 514 345 4801 ; sylvain.chemtob@umontreal.ca ; js.joyal@umontreal.ca.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Joyal
authors.forename: Vikrant K
authors.initials: VK
authors.lastname: Bhosle
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: F2rl1; G-protein coupled receptor; angiogenesis; cell nucleus; intracrine signaling