title: Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid.
abstract: Hydroxy fatty acids are critical lipid mediators involved in various pathophysiologic functions. We cloned and identified GPR31, a plasma membrane orphan G protein-coupled receptor that displays high affinity for the human 12-lipoxygenase-derived product 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE). Thus, GPR31 is named 12-(S)-HETE receptor (12-HETER) in this study. The cloned 12-HETER demonstrated high affinity binding for 12-(S)-[(3)H]HETE (K(d) = 4.8 ± 0.12 nm). Also, 12-(S)-HETE efficiently and selectively stimulated GTPγS coupling in the membranes of 12-HETER-transfected cells (EC(50) = 0.28 ± 1.26 nm). Activating GTPγS coupling with 12-(S)-HETE proved to be both regio- and stereospecific. Also, 12-(S)-HETE/12-HETER interactions lead to activation of ERK1/2, MEK, and NFκB. Moreover, knocking down 12-HRTER specifically inhibited 12-(S)-HETE-stimulated cell invasion. Thus, 12-HETER represents the first identified high affinity receptor for the 12-(S)-HETE hydroxyl fatty acids.
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48202, USA.
authors.forename: Yande
authors.initials: Y
authors.lastname: Guo
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhang
authors.forename: Craig
authors.initials: C
authors.lastname: Giroux
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Cai
authors.forename: Prasanna
authors.initials: P
authors.lastname: Ekambaram
authors.forename: Ashok-Kumar
authors.initials: AK
authors.lastname: Dilly
authors.forename: Andrew
authors.initials: A
authors.lastname: Hsu
authors.forename: Senlin
authors.initials: S
authors.lastname: Zhou
authors.forename: Krishna Rao
authors.initials: KR
authors.lastname: Maddipati
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Joshi
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Tucker
authors.forename: Menq-Jer
authors.initials: MJ
authors.lastname: Lee
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: Honn
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C501953:GPR31 protein, human; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020930:MAP Kinase Kinase Kinases