title: Competing functions encoded in the allergy-associated F(c)epsilonRIbeta gene.
abstract: Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, F(c)epsilonRI. In humans, F(c)epsilonRI is expressed as a tetramer (alphabetagamma(2)) and a trimer (alphagamma(2)). The beta subunit is an amplifier of F(c)epsilonRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the F(c)epsilonRIbeta gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical beta, the other a novel truncated form, beta(T). In contrast to beta, beta(T) prevents F(c)epsilonRI surface expression by inhibiting alpha chain maturation. Moreover, beta(T) competes with beta to control F(c)epsilonRI surface expression in vitro. We propose that the relative abundance of the products of the beta gene may control the level of F(c)epsilonRI surface expression and thereby influence susceptibility to allergic diseases.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Donnadieu
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Jouvin
authors.forename: Shalini
authors.initials: S
authors.lastname: Rana
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: Ester H
authors.initials: EH
authors.lastname: Mockford
authors.forename: William O
authors.initials: WO
authors.lastname: Cookson
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kinet
mesh_terms: D017398:Alternative Splicing; D001491:Basophils / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005809:Genes, Regulator; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000276:immunology; D020836:Protein Structure, Quaternary; D017455:Receptors, IgE / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D017455:Receptors, IgE