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Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor.
Journal article

Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor.

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  • 2002-07-02
Published in:
  • American journal of respiratory cell and molecular biology. - 2002
Alternative Splicing
Binding Sites
Cells, Cultured
Dimerization
Exons
Fibroblasts
Humans
Interleukin-6
Lung
Models, Molecular
Protein Biosynthesis
Protein Isoforms
RNA, Messenger
Receptors, Interleukin-6
English Interleukin (IL)-6 is a multifunctional cytokine showing a wide variety of biologic functions on various tissues. Extracellular IL-6 signals through heterohexameric complex formation with IL-6 receptor-alpha (IL-6Ralpha) and IL-6 receptor-beta (IL-6Rbeta). In analogy to cytokines IL-2 and IL-4, we investigated the expression of IL-6 splice variants in lung tissue and cultivated fibroblasts. In human lung specimens, four different IL-6 transcripts were characterized as follows: native IL-6; IL-6 missing either exon 2 (IL-6Delta2), exon 4 (IL-6Delta4), or missing both; and exons 2 and 4 (IL-6Delta2,4). Only native IL-6 and IL-6Delta4 encoded for proteins of ~ 26 and 17 kD, respectively. Although the overall structure and most functional sites of the IL-6Delta4 protein were predicted to be maintained, IL-6Delta4 was found to lack two amino acids necessary for IL-6/IL-6 homodimerization as well as two of the six amino acids required for interaction with IL-6Rbeta. Receptor mobility shift assays confirmed that the new isoform formed a stable complex with IL-6Ralpha; however, no interaction with IL-6Rbeta was observed. Thus, IL-6Delta4 is likely to compete with native IL-6 for IL-6Ralpha binding but fails to transmit IL-6Rbeta-mediated signaling.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/4603
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