TY - JOUR
T1 - Fringe modulation of Jagged1-induced Notch signaling requires the action of β4galactosyltransferase-1
AU - Chen, J.
AU - Moloney, D. J.
AU - Stanley, P.
PY - 2001/11/20
Y1 - 2001/11/20
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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U2 - 10.1073/pnas.241398098
DO - 10.1073/pnas.241398098
M3 - Article
C2 - 11707585
AN - SCOPUS:0035923524
SN - 0027-8424
VL - 98
SP - 13716
EP - 13721
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24
ER -