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    Blood. 2010 Nov 4;116(18):3677-80. Epub 2010 Jul 21.

    Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2.

    Mitola S, Ravelli C, Moroni E, Salvi V, Leali D, Ballmer-Hofer K, Zammataro L, Presta M.

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    Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, Brescia, Italy.

    Abstract

    The bone morphogenic protein antagonist gremlin is expressed during embryonic development and under different pathologic conditions, including cancer. Gremlin is a proangiogenic protein belonging to the cystine-knot superfamily that includes transforming growth factor-β proteins and the angiogenic vascular endothelial growth factors (VEGFs). Here, we demonstrate that gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals, in a bone morphogenic protein-independent manner. Similar to VEGF-A, gremlin activates VEGFR2 in endothelial cells, leading to VEGFR2-dependent angiogenic responses in vitro and in vivo. Gremlin thus represents a novel proangiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization.

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    PMID:
    20660291
    [PubMed - indexed for MEDLINE]
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