Abstract
Semaphorins are a large family of molecular cues implicated in neural development and in a variety of functions outside the nervous system. Semaphorin 5A (Sema5A) is a transmembrane semaphorin, containing seven thrombospondin type-1 repeats, which was recently found to control axon guidance. Here we show that plexin-B3 is a high-affinity receptor specific for Sema5A. We further demonstrate that plexin-B3 activation by Sema5A mediates functional responses in plexin-B3-expressing cells (either fibroblasts, epithelial and primary endothelial cells). In addition, Sema5A can trigger the intracellular signalling of the hepatocyte growth factor/scatter factor receptor, Met, associated in a complex with plexin-B3. We thus conclude that Sema5A is able to elicit multiple functional responses through its receptor plexin-B3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / metabolism
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Blotting, Western
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COS Cells
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Cell Line
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Cell Membrane / metabolism
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Cell Movement
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Dose-Response Relationship, Drug
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Endothelium, Vascular / embryology
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology
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Epithelial Cells / metabolism
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Fibroblasts / metabolism
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Humans
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Immunoprecipitation
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Kinetics
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism
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Mice
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NIH 3T3 Cells
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / physiology
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Neural Cell Adhesion Molecules / metabolism*
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Neural Cell Adhesion Molecules / physiology
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Protein Binding
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Proto-Oncogene Proteins c-met / metabolism
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RNA, Small Interfering / metabolism
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Receptors, Cell Surface / metabolism
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Semaphorins
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Signal Transduction
Substances
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Membrane Proteins
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Nerve Tissue Proteins
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Neural Cell Adhesion Molecules
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PLXNB3 protein, human
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RNA, Small Interfering
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Receptors, Cell Surface
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SEMA5A protein, human
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Semaphorins
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Proto-Oncogene Proteins c-met