Signal transduction of interleukin-11 and interleukin-6 α-receptors

The cytokines Interleukin (IL)-11 and IL-6 are important mediators that regulate differentiation and proliferation of immune cells. Both cytokines bind to unique non-signaling α-receptors (IL-11R and IL-6R, respectively), and the resulting cytokine/cytokine receptor complexes recruit a homodimer of the signal-transducing β-receptor glycoprotein (gp)130. Gp130 is expressed ubiquitously, whereas both α-receptors show a celland tissue-specific expression pattern, thus determining cellular responsiveness towards IL-6 and/or IL-11. Formation of the signaling complexes activates intracellular signaling cascades, most prominently the Janus kinase (Jak)/Signal Transducer and Activator of Transcription (STAT) pathway. In a recent paper published in Biochimie, we analyzed the signaling capacity of eight chimeric receptors consisting of different domains of IL-11R and IL-6R. Our results showed that the intracellular region, the transmembrane region or the stalk region can be swapped between the two receptors, as they are not essential to discriminate between the two cytokines. Selectivity of the two receptors is exclusively warranted by the cytokine binding module (CBM), which resides within the domains D1 to D3. These results underline a modular organization of IL-11R and IL-6R and a comparable signal transduction of both cytokines.