Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 32, Pages 22140-22150Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.560938
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft (Bonn, Germany) [SCHE 907/2-1]
- Ferring Pharmaceuticals A/S (Copenhagen, Denmark)
Ask authors/readers for more resources
Interleukin (IL)-6 signals via a receptor complex composed of the signal-transducing beta-receptor gp130 and the non-signaling membrane-bound or soluble IL-6 receptor alpha (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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available