Abstract
Y-box (YB) protein-1 is secreted by mesangial and immune cells after cytokine challenge, but extracellular functions are unknown. Here, we demonstrate that extracellular YB-1 associates with outer cell membrane components and interacts with extracellular Notch-3 receptor domains. The interaction appears to be specific for Notch-3, as YB-1-green fluorescent protein binds to the extracellular domains and full-length forms of Notch-3 but not to Notch-1. YB-1-green fluorescent protein and Notch-3 proteins co-localize at cell membranes, and extracellular YB-1 activates Notch-3 signaling, resulting in nuclear translocation of the Notch-3 intracellular domain and up-regulation of Notch target genes. The YB-1/Notch-3 interaction may be of particular relevance for inflammatory mesangioproliferative disease, as both proteins co-localize in an experimental nephritis model and receptor activation temporally and spatially correlates with YB-1 expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Cell Line
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Cell Membrane / metabolism
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Cell Nucleus / metabolism
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Gene Expression
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Glomerulonephritis, Membranoproliferative / genetics
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Glomerulonephritis, Membranoproliferative / metabolism
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Glomerulonephritis, Membranoproliferative / pathology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Immunoblotting
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Immunohistochemistry
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Immunoprecipitation
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Kidney / metabolism
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Kidney / pathology
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Ligands
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Male
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Mice
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Microscopy, Confocal
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Microscopy, Fluorescence
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Protein Binding
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Rats
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Rats, Wistar
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Receptor, Notch3
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transfection
Substances
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Ligands
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Notch3 protein, mouse
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Receptor, Notch3
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Receptors, Notch
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Transcription Factors
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YB-1 protein, mouse
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Green Fluorescent Proteins