Identification of a Novel IL-6 Isoform Binding to the Endogenous IL-6 Receptor
作者： Michel P. Bihl , Karl Heinimann , Jochen J. Rüdiger , Oliver Eickelberg , André P. Perruchoud
关键词:
摘要: Interleukin (IL)-6 is a multifunctional cytokine showing wide variety of biologic functions on various tissues. Extracellular IL-6 signals through heterohexameric complex formation with receptor-alpha (IL-6Ralpha) and receptor-beta (IL-6Rbeta). In analogy to cytokines IL-2 IL-4, we investigated the expression splice variants in lung tissue cultivated fibroblasts. human specimens, four different transcripts were characterized as follows: native IL-6; missing either exon 2 (IL-6Delta2), 4 (IL-6Delta4), or both; exons (IL-6Delta2,4). Only IL-6Delta4 encoded for proteins ~ 26 17 kD, respectively. Although overall structure most functional sites protein predicted be maintained, was found lack two amino acids necessary IL-6/IL-6 homodimerization well six required interaction IL-6Rbeta. Receptor mobility shift assays confirmed that new isoform formed stable IL-6Ralpha; however, no IL-6Rbeta observed. Thus, likely compete IL-6Ralpha binding but fails transmit IL-6Rbeta-mediated signaling.
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