IL-6-induced classic and trans-signalling
IL-6 can activate cells in two ways. In classic signalling, IL-6 binds to the membrane-bound IL-6 receptor α (IL-6Rα) and to gp130, resulting in an anti-inflammatory response. In contrast, binding of IL-6 to the soluble isoform of IL-6Rα and gp130 also allows stimulation of cells that do not express IL-6Rα. This stimulation, known as trans-signalling, triggers a pro-inflammatory response. In cooperation with the research groups of Prof. Garbers (Magdeburg), Prof. Rose-John (Kiel), Prof. Scheller (Düsseldorf) and Prof. Findeisen/ Prof. Streif (both formerly Magdeburg), and the industrial partner CONARIS Research Institute AG (Kiel), we investigated how classic and trans-signalling are reflected in signal transduction and which molecules and processes control the different signal transduction patterns within the framework of the BMBF-funded E-bio project InTraSig (Inhibiting Trans-Signalling). We showed that the dynamics of intracellular signal transduction is determined by the stoichiometry of the receptor subunits. These results support the development of specific trans-signalling inhibitors, which represent promising therapies against inflammatory diseases.
.
