title: Alternative intronic polyadenylation generates the interleukin-6 trans-signaling inhibitor sgp130-E10.
abstract: Interleukin (IL)-6 signals via a receptor complex composed of the signal-transducing β-receptor gp130 and the non-signaling membrane-bound or soluble IL-6 receptor α (IL-6R, sIL-6R), which is referred to as classic and trans-signaling, respectively. IL-6 trans-signaling is functionally associated with the development of chronic inflammatory diseases and cancer. Soluble gp130 (sgp130) variants are natural inhibitors of trans-signaling. Differential splicing yields sgp130 isoforms. Here, we describe that alternative intronic polyadenylation in intron 10 of the gp130 transcript results in a novel mRNA coding for an sgp130 protein isoform (sgp130-E10) of 70-80 kDa. The sgp130-E10 protein was expressed in vivo in human peripheral blood mononuclear cells. To assess the biological activity of sgp130-E10, we expressed this variant as Fc-tagged fusion protein (sgp130-E10Fc). Recombinant sgp130-E10Fc binds to a complex of IL-6 and sIL-6R, but not to IL-6 alone, and specifically inhibits IL-6 trans-signaling. Thus, it might play an important role in the regulation of trans-signaling in vivo.
authors: From the Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf.
authors: Jan
authors: J
authors: Sommer
authors: the Institute of Biochemistry, Medical Faculty, Christian-Albrechts-University, 24118 Kiel.
authors: Christoph
authors: C
authors: Garbers
authors: the Institute of Biochemistry, Medical Faculty, Christian-Albrechts-University, 24118 Kiel.
authors: Janina
authors: J
authors: Wolf
authors: the Institute of Biochemistry, Medical Faculty, Christian-Albrechts-University, 24118 Kiel.
authors: Ahmad
authors: A
authors: Trad
authors: From the Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf.
authors: Jens M
authors: JM
authors: Moll
authors: the Institute of Molecular Biotechnology, RWTH Aachen University, 52062 Aachen, and.
authors: Markus
authors: M
authors: Sack
authors: the Institute of Molecular Biotechnology, RWTH Aachen University, 52062 Aachen, and.
authors: Rainer
authors: R
authors: Fischer
authors: the Institute of Biochemistry, Medical Faculty, Christian-Albrechts-University, 24118 Kiel.
authors: Joachim
authors: J
authors: Grötzinger
authors: CONARIS Research Institute AG, 24118 Kiel, Germany.
authors: Georg H
authors: GH
authors: Waetzig
authors: From the Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf.
authors: Doreen M
authors: DM
authors: Floss
authors: From the Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, jscheller@uni-duesseldorf.de.
authors: Jürgen
authors: J
authors: Scheller
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D050822:Cytokine Receptor gp130 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000378:metabolism*; D007438:Introns; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D026723:Polyadenylation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility
chemical_list: C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D046912:Multiprotein Complexes; D020033:Protein Isoforms; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130
keywords: Alternative Splicing; Interleukin; Polyadenylation; Protein-tyrosine Kinase (Tyrosine Kinase); Signal Transduction