Competing functions encoded in the allergy-associated F(c)epsilonRIbeta gene.
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.
Donnadieu
Emmanuel
E
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Jouvin
Marie-Hélène
MH
Rana
Shalini
S
Moffatt
Miriam F
MF
Mockford
Ester H
EH
Cookson
William O
WO
Kinet
Jean-Pierre
JP
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*
D020033:Protein Isoforms; D017455:Receptors, IgE