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Zusammenfassung:

Intracellular signaling cascades, e.g. the Jak/STAT pathway, have several different functions in health and disease. Their activation and the duration of signaling must be tightly controlled. Dysregulated, overshooting activities of such pathways are often associated with human diseases. The pleiotropic cytokines Interleukin-11 (IL-11) and IL-6 are secreted glycoproteins that activate their target cells via specific membrane-bound IL-6/IL-11 alpha receptors (IL-11R and IL-6R, respectively). Formation of cytokine/cytokine receptor complexes leads to the formation of a homodimer of the ubiquitously expressed signal-transducing beta-receptor gp130 (termed classic signaling), which induces signaling cascades like the Jak/STAT pathway. Thus, the cellular expression pattern of the alpha receptors determines which cells respond to IL-6 and IL-11, respectively, as gp130 is ubiquitously expressed. Importantly, the ectodomains of the IL-11R and IL-6R can be cleaved off the cells by several proteases, albeit with different preferences and specificities. The resulting soluble receptors (sIL-11R and sIL-6R) act as agonists and can activate cells via gp130 (termed trans-signaling), which widens the spectrum of cells that can be activated by IL-11 and IL-6. The presentation will give an overview how signaling on the inside is regulated by cytokine receptors on the outside of the cell, and how knowledge about these processes can be exploited therapeutically.

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