التفاصيل البيبلوغرافية
| العنوان: |
Engineered interleukin-6-derived cytokines recruit artificial receptor complexes and disclose CNTF signaling via the OSMR. |
| المؤلفون: |
Rafii, Puyan1, Cruz, Patricia Rodrigues1, Ettich, Julia1, Seibel, Christiane1, Padrini, Giacomo1, Wittich, Christoph1, Lang, Alexander2, Petzsch, Patrick3, Köhrer, Karl3, Moll, Jens M.1, Floss, Doreen M.1, Scheller, Jürgen1 jscheller@uni-duesseldorf.de |
| المصدر: |
Journal of Biological Chemistry. May2024, Vol. 300 Issue 5, p1-15. 15p. |
| مصطلحات موضوعية: |
*LEUKEMIA inhibitory factor, *ONCOSTATIN M, *SYNTHETIC receptors, *INSULIN resistance, *CYTOKINES, *BINDING sites |
| مستخلص: |
Ciliary neurotrophic factor (CNTF) activates cells via the non-signaling α-receptor CNTF receptor (CNTFR) and the two signaling β-receptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR). The CNTF derivate, Axokine, was protective against obesity and insulin resistance, but clinical development was halted by the emergence of CNTF antibodies. The chimeric cytokine IC7 used the framework of interleukin (IL-)6 with the LIFR-binding site from CNTF to activate cells via IL-6R:gp130:LIFR complexes. Similar to CNTF/Axokine, IC7 protected mice from obesity and insulin resistance. Here, we developed CNTF-independent chimeras that specifically target the IL-6R:gp130:LIFR complex. In GIL-6 and GIO-6, we transferred the LIFR binding site from LIF or OSM to IL-6, respectively. While GIO-6 signals via gp130:IL6R:LIFR and gp130:IL-6R:OSMR complexes, GIL-6 selectively activates the IL-6R:gp130:LIFR receptor complex. By reevaluation of IC7 and CNTF, we discovered the Oncostatin M receptor (OSMR) as an alternative non-canonical high-affinity receptor leading to IL-6R:OSMR:gp130 and CNTFR:OSMR:gp130 receptor complexes, respectively. The discovery of OSMR as an alternative high-affinity receptor for IC7 and CNTF designates GIL-6 as the first truly selective IL6R:gp130:LIFR cytokine, whereas GIO-6 is a CNTF-free alternative for IC7. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder