1. Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.
- Author
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Mitsuyasu H, Yanagihara Y, Mao XQ, Gao PS, Arinobu Y, Ihara K, Takabayashi A, Hara T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin JM, and Izuhara K
- Subjects
- Amino Acid Substitution, Animals, B-Lymphocytes immunology, B-Lymphocytes metabolism, Base Sequence, Cell Line, Humans, Hypersensitivity, Immediate genetics, Hypersensitivity, Immediate immunology, Mice, Mutagenesis, Site-Directed, Oligonucleotide Probes genetics, Promoter Regions, Genetic, Protein Conformation, Receptors, IgE metabolism, Receptors, Interleukin-4 chemistry, Receptors, Interleukin-4 metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, STAT6 Transcription Factor, Signal Transduction, Trans-Activators metabolism, Transfection, Genetic Variation, Immunoglobulin E biosynthesis, Receptors, Interleukin-4 genetics
- Abstract
Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.
- Published
- 1999