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- 저자 : John B. Lowe (검색결과 1 건)
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The role of O-fucosylated glycans in Notch signaling
Jeongsup Shim,Bronislawa Petryniak,John B. Lowe 한국당과학회 2013 한국당과학회 학술대회 Vol.2013 No.1
Signaling from the Notch receptor family is important in development, and its role in disease has assigned the Notch signaling pathway as a therapeutic target (1). Mammalian Notch receptors are single-pass transmembrane glycoproteins containing 29-36 EGF-like repeats. Notch receptors on receiving cells signal when they interact with Notch ligands expressed on sending cells. Glycosylation of some Notch EGF-like repeats modulates signaling (2). EGF repeat glycosylation includes constitutive fucosylation of some EGF repeat-localized serine/threonine residues, and elongation of fucose-initiated glycans regulated by the Fringe family of glycosyltransferases (3). We sought to determine how O-fucosylated glycans modulate Notch signaling, using cell-based Notch signaling assay by co-culturing with Notch ligand bearing cells and beads and protein-protein binding assay with surface plasmon resonance (SPR). We find that lunatic Fringe modification of Notch1 receptors enhances Dll1, Dll4, and Jag2 binding affinities and signaling, while it reduces Jag1-mediated binding affinity and signaling. SPR study indicates that Notch signaling is correlated with association constant (KA) and maximum binding capacity (Rmax) may be critical in Notch signaling from Jag2 in solid-phase Notch signaling assay.
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