TY - JOUR
T1 - Modulation of receptor signaling by glycosylation
T2 - Fringe is an O-fucose-β1,3-N-acetylglucosaminyltransferase
AU - Haltiwanger, Robert S.
AU - Stanley, Pamela
N1 - Funding Information:
The authors thank Li Shao, Daniel Moloney, Jihua Chen, Vlad Panin, Ken Irvine, Tom Vogt, and Stuart Johnston for their contributions and collaboration in the work on fringe. Original work was supported by grants to RSH (NIH GM61126) and PS (NIH RO1 CA 36434 and the Mizutani Foundation).
PY - 2002/12/19
Y1 - 2002/12/19
N2 - 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.
AB - 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.
KW - Fringe
KW - N-acetylglucosaminyltransferase
KW - Notch
KW - O-fucose
KW - Signal transduction
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U2 - 10.1016/S0304-4165(02)00400-2
DO - 10.1016/S0304-4165(02)00400-2
M3 - Review article
C2 - 12417415
AN - SCOPUS:0037137482
SN - 0304-4165
VL - 1573
SP - 328
EP - 335
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -