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). It 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). Recent results have shown that fringe modulates Notch activity by altering the structure of the O-fucose glycans on the 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-G-G-S/T-C3, where X can be any amino acid and S/T is the modification site (Harris and Spellman 1993). Numerous cell surface and secreted proteins have EGF repeats containing these sites. Fringe catalyzes the addition of a β-linked GlcNAc to the 3′-hydroxyl of O-fucose, which can be further elongated to a tetrasaccharide with the structure NeuAcα2-3/ 6Galβ1-4GlcNAcβ1-3Fuc (Harris and Spellman 1993; Moloney et al. 2000a; Moloney et al. 2000b). The glycosyltransferase activity of fringe is essential for its ability to modulate Notch signaling (Bruckner et al. 2000; Moloney et al. 2000a; Munro and Freeman 2000), demonstrating that signal transduction events can be regulated by alterations in the glycosylation state of receptors.
KeywordsNotch Signaling Notch Receptor Notch Activation Wing Imaginal Disc Glycosyltransferase Activity
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- Blair SS (2000) Notch signaling: Fringe really is a glycosyltransferase. Curr Biol 10: R608-R612Google Scholar