Functional characterisation of W147A: a high-affinity interleukin-11 antagonist

Nicholas Underhill-Day, Lisa McGovern, N Karpovich, HJ Mardon, VA Barton, John Heath

Research output: Contribution to journalArticle

30 Citations (Scopus)


IL-11 is a member of the gp130 family of cytokines, which signal via assembly of multisubunit receptor complexes containing at least one molecule of the transmembrane signaling receptor gp130. IL-11 forms a high-affinity complex, thereby inducing gp130-dependent signaling. Previous studies have identified three distinct receptor binding sites, I, II, and III, crucial for the binding of murine IL-11 (mIL-11) to both the IL-11R and gp130. In this study, we have further characterized the role of the mIL-11 site III mutant W147A. We show that W147A is a high-affinity specific antagonist of mIL-11-mediated signaling in gp130/IL-11R-transfected Ba/F3 cells. The antagonistic action of W147A is due to its ability to competitively disrupt multimeric gp130/IL-11R signaling complex formation. We also show that W147A inhibits IL-11-mediated signaling in primary human endometrial cells, thus demonstrating the potential utility of W147A in suppressing IL-11 responses in vivo.
Original languageEnglish
Pages (from-to)3406-3414
Number of pages9
Issue number8
Early online date15 May 2003
Publication statusPublished - 15 May 2003


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