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    PLoS One. 2008;3(10):e3452. Epub 2008 Oct 20.

    A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11.

    Cardó-Vila M, Zurita AJ, Giordano RJ, Sun J, Rangel R, Guzman-Rojas L, Anobom CD, Valente AP, Almeida FC, Lahdenranta J, Kolonin MG, Arap W, Pasqualini R.

    Source

    The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

    Abstract

    Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11R alpha is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11R alpha has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs.

    PMID:
    18941632
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2565473
    Free PMC Article

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