YB-1 Acts as a Ligand for Notch-3 Receptors and Modulates Receptor Activation

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 app...

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Bibliographic Details
Published in:The Journal of biological chemistry 2009-09, Vol.284 (39), p.26928-26940
Main Authors: Rauen, Thomas, Raffetseder, Ute, Frye, Björn C., Djudjaj, Sonja, Mühlenberg, Philipp J.T., Eitner, Frank, Lendahl, Urban, Bernhagen, Jürgen, Dooley, Steven, Mertens, Peter R.
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cell Line
Cell Membrane - metabolism
Cell Nucleus - metabolism
Gene Expression
Glomerulonephritis, Membranoproliferative - genetics
Glomerulonephritis, Membranoproliferative - metabolism
Glomerulonephritis, Membranoproliferative - pathology
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Humans
Immunoblotting
Immunohistochemistry
Immunoprecipitation
Kidney - metabolism
Kidney - pathology
Ligands
Male
Mechanisms of Signal Transduction
Mice
Microscopy, Confocal
Microscopy, Fluorescence
Protein Binding
Rats
Rats, Wistar
Receptor, Notch3
Receptors, Notch - genetics
Receptors, Notch - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
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Description
Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.046599