Fringe modulation of Jagged1-induced Notch signaling requires the action of β4galactosyltransferase-1

J. Chen, D. J. Moloney, Pamela Stanley

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121 Citations (Scopus)

Abstract

Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a β3N-acetylglucosaminyltransferase (β3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamster ovary cell glycosylation mutants to identify a key aspect of the mechanism of fringe action. Although the β3GlcNAcT activity of manic or lunatic fringe is shown to be necessary for inhibition of Jagged1-induced Notch signaling in a coculture assay, it is not sufficient. Fringe fails to inhibit Notch signaling if the disaccharide generated by fringe action, GlcNAcβ3Fuc, is not elongated. The trisaccharide, Galβ4GlcNAcβ3Fuc, is the minimal O-fucose glycan to support fringe modulation of Notch signaling. Of six β4galactosyltransferases (β4GAlT) in Chinese hamster ovary cells, only β4GalT-1 is required to add GaI to GlcNAcβ3Fuc, identifying β4GAlT-1 as a new modulator of Notch signaling.

Original languageEnglish (US)
Pages (from-to)13716-13721
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number24
DOIs
StatePublished - Nov 20 2001

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Fucose
Cricetulus
Ovary
Trisaccharides
Disaccharides
Coculture Techniques
Glycosylation
Epidermal Growth Factor
Polysaccharides

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Fringe modulation of Jagged1-induced Notch signaling requires the action of β4galactosyltransferase-1",
abstract = "Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a β3N-acetylglucosaminyltransferase (β3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamster ovary cell glycosylation mutants to identify a key aspect of the mechanism of fringe action. Although the β3GlcNAcT activity of manic or lunatic fringe is shown to be necessary for inhibition of Jagged1-induced Notch signaling in a coculture assay, it is not sufficient. Fringe fails to inhibit Notch signaling if the disaccharide generated by fringe action, GlcNAcβ3Fuc, is not elongated. The trisaccharide, Galβ4GlcNAcβ3Fuc, is the minimal O-fucose glycan to support fringe modulation of Notch signaling. Of six β4galactosyltransferases (β4GAlT) in Chinese hamster ovary cells, only β4GalT-1 is required to add GaI to GlcNAcβ3Fuc, identifying β4GAlT-1 as a new modulator of Notch signaling.",
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AU - Chen, J.

AU - Moloney, D. J.

AU - Stanley, Pamela

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N2 - Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a β3N-acetylglucosaminyltransferase (β3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamster ovary cell glycosylation mutants to identify a key aspect of the mechanism of fringe action. Although the β3GlcNAcT activity of manic or lunatic fringe is shown to be necessary for inhibition of Jagged1-induced Notch signaling in a coculture assay, it is not sufficient. Fringe fails to inhibit Notch signaling if the disaccharide generated by fringe action, GlcNAcβ3Fuc, is not elongated. The trisaccharide, Galβ4GlcNAcβ3Fuc, is the minimal O-fucose glycan to support fringe modulation of Notch signaling. Of six β4galactosyltransferases (β4GAlT) in Chinese hamster ovary cells, only β4GalT-1 is required to add GaI to GlcNAcβ3Fuc, identifying β4GAlT-1 as a new modulator of Notch signaling.

AB - Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a β3N-acetylglucosaminyltransferase (β3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamster ovary cell glycosylation mutants to identify a key aspect of the mechanism of fringe action. Although the β3GlcNAcT activity of manic or lunatic fringe is shown to be necessary for inhibition of Jagged1-induced Notch signaling in a coculture assay, it is not sufficient. Fringe fails to inhibit Notch signaling if the disaccharide generated by fringe action, GlcNAcβ3Fuc, is not elongated. The trisaccharide, Galβ4GlcNAcβ3Fuc, is the minimal O-fucose glycan to support fringe modulation of Notch signaling. Of six β4galactosyltransferases (β4GAlT) in Chinese hamster ovary cells, only β4GalT-1 is required to add GaI to GlcNAcβ3Fuc, identifying β4GAlT-1 as a new modulator of Notch signaling.

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