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Fringe (UDP-GlcNAc: O-Fucosylpeptide ß1,3 N-Acetylglucosaminyltransferase)

Reference work entry

Abstract

Fringe provides a clear example of the role that carbohydrate modifications can play in regulating signal transduction events. Fringe was originally identified for its role in dorsal/ventral boundary formation during Drosophila wing development (Irvine and Wieschaus 1994). Fringe functions by altering the response of the Notch receptor to its ligands, potentiating signaling from Delta and inhibiting that from Serrate (Fleming et al. 1997; Panin et al. 1997). Fringe modulates Notch activity by altering the structure of the O-fucose glycans on the Epidermal Growth Factor-like (EGF) repeats in the extracellular domain of Notch (Bruckner et al. 2000; Moloney et al. 2000a). O-Fucose modifications occur between the second and third conserved cysteines of an EGF repeat at the consensus site C2-X-X-X-X-(S/T)-C3, where X can be any amino acid and S/T is the modification site (Rana and Haltiwanger 2011). Numerous cell surface and secreted proteins have EGF repeats containing these sites. Fringe catalyzes the addition of a ß-linked GlcNAc to the 3′-hydroxyl of O-fucose, which can be further elongated to a tetrasaccharide with the structure NeuAcα2-3/6Galß1-4GlcNAcß1-3Fuc in mammals (Moloney et al. 2000b; Rana and Haltiwanger 2011), but only to the disaccharide GlcNAcß1-3Fuc in flies (Xu et al. 2007). The glycosyltransferase activity of fringe is essential for its ability to modulate Notch signaling (Bruckner et al. 2000; Moloney et al. 2000a), demonstrating that signal transduction events can be regulated by alterations in the glycosylation state of receptors.

Keywords

Notch Signaling Notch Receptor Notch Activity Acceptor Substrate Human Genetic Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of Biochemistry and Cell BiologyStony Brook UniversityStony BrookUSA

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