Bihl MP Heinimann K Rüdiger JJ Eickelberg O Perruchoud AP Tamm M Roth M 2002 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. https://sonar.ch/global/documents/4603 eng info:eu-repo/semantics/altIdentifier/doi/10.1165/ajrcmb.27.1.4637 info:eu-repo/semantics/altIdentifier/pmid/12091245 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 Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor. http://purl.org/coar/resource_type/c_6501