Role of proteolysis in interleukin-11 signaling (A10)

该项目涉及IL-11，它可以通过膜结合的IL-11受体的ADAM10裂解片段激活细胞，这一过程被称为IL-11反式信号转导。将分析ADAM10对IL-11R蛋白降解的调节，菱形和其他蛋白酶对IL-11R的切割，以及IL-11经典信号和反式信号的功能作用。IL-11在结肠癌中的作用将得到解决，并将开发新的ADAM10抑制剂，使其能够以细胞特异性的方式阻止ADAM10介导的IL-11R裂解。

The project deals with IL-11, which can activate cells through an ADAM10-cleaved fragment of the membrane bound IL-11 receptor, a process that has been termed IL-11 trans-signaling. The regulation of IL-11R proteolysis by ADAM10, the cleavage of the IL-11R by rhomboid and other proteases and the functional role of IL-11 classic and trans-signaling will be analyzed. The role of IL-11 in colon cancer will be addressed and novel inhibitors of ADAM10 will be developed that will allow to block ADAM10-mediated IL-11R cleavage in a cell specific manner.