title: Structure, function and pathophysiology of protease activated receptors.
abstract: Discovered in the 1990s, protease activated receptors(1) (PARs) are membrane-spanning cell surface proteins that belong to the G protein coupled receptor (GPCR) family. A defining feature of these receptors is their irreversible activation by proteases; mainly serine. Proteolytic agonists remove the PAR extracellular amino terminal pro-domain to expose a new amino terminus, or tethered ligand, that binds intramolecularly to induce intracellular signal transduction via a number of molecular pathways that regulate a variety of cellular responses. By these mechanisms PARs function as cell surface sensors of extracellular and cell surface associated proteases, contributing extensively to regulation of homeostasis, as well as to dysfunctional responses required for progression of a number of diseases. This review examines common and distinguishing structural features of PARs, mechanisms of receptor activation, trafficking and signal termination, and discusses the physiological and pathological roles of these receptors and emerging approaches for modulating PAR-mediated signaling in disease.
authors.affiliation: Mater Medical Research Institute, Aubigny Place, Raymond Terrace, South Brisbane Qld 4101, Australia.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Adams
authors.forename: Rithwik
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Mei-Kwan
authors.initials: MK
authors.lastname: Yau
authors.forename: Jacky Y
authors.initials: JY
authors.lastname: Suen
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: John D
authors.initials: JD
authors.lastname: Hooper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000639:trends; D003324:Coronary Artery Disease / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D044462:Receptors, Proteinase-Activated / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D044462:Receptors, Proteinase-Activated