Modulation of receptor signaling by glycosylation: Fringe is an O-fucose-β1,3-N-acetylglucosaminyltransferase

Robert S. Haltiwanger, Pamela Stanley

Research output: Contribution to journalReview article

85 Scopus citations

Abstract

The Notch family of signaling receptors plays key roles in determining cell fate and growth control. Recently, a number of laboratories have shown that O-fucose glycans on the epidermal growth factor (EGF)-like repeats of the Notch extracellular domain modulate Notch signaling. Fringe, a known modifier of Notch function, is an O-fucose specific β1,3-N-acetylglucosaminyltransferase. The transfer of GlcNAc to O-fucose on Notch by fringe results in the potentiation of signaling by the Delta class of Notch ligands, but causes inhibition of signaling by the Serrate/Jagged class of Notch ligands. Interestingly, addition of a β1,4 galactose by β4GalT-1 to the GlcNAc added by fringe is required for Jagged1-induced Notch signaling to be inhibited in a co-culture assay. Thus, both fringe and β4GalT-1 are modulators of Notch function. Several models have been proposed to explain how alterations in O-fucose glycans result in changes in Notch signaling, and these models are discussed.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1573
Issue number3
DOIs
StatePublished - Dec 19 2002

Keywords

  • Fringe
  • N-acetylglucosaminyltransferase
  • Notch
  • O-fucose
  • Signal transduction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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