title: Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts.
abstract: Dysfunction of receptors for IgG (FcgammaRs) has been thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described SLE-associated polymorphism of FcgammaRIIb (FcgammaRIIbT(232)), encoding a single transmembrane amino acid substitution, is functionally impaired. FcgammaRIIbT(232) is unable to inhibit activatory receptors because it is excluded from sphingolipid rafts, resulting in the unopposed proinflammatory signaling thought to promote SLE.
authors.affiliation: Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Cambridge CB2 2XY, UK. arf27@cam.ac.uk
authors.forename: R Andres
authors.initials: RA
authors.lastname: Floto
authors.forename: Menna R
authors.initials: MR
authors.lastname: Clatworthy
authors.forename: Karen R
authors.initials: KR
authors.lastname: Heilbronn
authors.forename: Dalya R
authors.initials: DR
authors.lastname: Rosner
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
authors.forename: Angela
authors.initials: A
authors.lastname: Rankin
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lehner
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.forename: Janet M
authors.initials: JM
authors.lastname: Allen
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008264:Macrophages / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020298:U937 Cells
chemical_list: D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG