The structure of the IL-11 signalling complex
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Cell signalling by IL-11 is initiated by binding of soluble IL-11 to its membrane bound, specific receptor, IL-11Rα. This binary complex subsequently engages with GP130, inducing GP130 dimerisation and resulting in activation of the transcription factor, Signal Transducer and Activator of Transcription (STAT)-3 (Figure 3). STAT3 has been implicated in the maintenance of a tumour-promoting, inflammatory microenvironment, and persistent STAT3 activation is a recurrent feature of many human cancers of both haematopoietic and epithelial origin, including colon cancer.
Figure 1: The IL-11/STAT3 signalling cascade leads to activation of STAT3 target genes associated with inflammation and the progression of colon cancer.
Despite its importance, our understanding of the structure of the authentic IL-11 signalling complex and the interactions between its components remains rudimentary. Our recent work has produced the first crystal structure and biophysical characterization of IL-11.
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