TY - JOUR
T1 - Roles of glycosylation in notch signaling
AU - Stanley, Pamela
AU - Okajima, Tetsuya
N1 - Funding Information:
The authors wish to thank their collaborators and lab members for their many contributions over the years. This work was supported by National Caner Institute grant RO1 95022 to P.S. and grants from the Japanese Ministry of Education, Science, Sports and Culture and Human Frontier Science Program to T.O.
PY - 2010
Y1 - 2010
N2 - Notch and the DSL Notch ligands Delta and Serrate/Jagged are glycoproteins with a single transmembrane domain. The extracellular domain (ECD) of both Notch receptors and Notch ligands contains numerous epidermal growth factor (EGF)-like repeats which are post-translationally modified by a variety of glycans. Inactivation of a subset of genes that encode glycosyltransferases which initiate and elongate these glycans inhibits Notch signaling. In the formation of developmental boundaries in Drosophila and mammals, in mouse T-cell and marginal zone B-cell development, and in co-culture Notch signaling assays, the regulation of Notch signaling by glycans is to date a cell-autonomous effect of the Notch-expressing cell. The regulation of Notch signaling by glycans represents a new paradigm of signal transduction. O-fucose glycans modulate the strength of Notch binding to DSL Notch ligands, while O-glucose glycans facilitate juxta-membrane cleavage of Notch, generating the substrate for intramembrane cleavage and Notch activation. Identifying precisely how the addition of particular sugars at specific locations on Notch modifies Notch signaling is a challenge for the future.
AB - Notch and the DSL Notch ligands Delta and Serrate/Jagged are glycoproteins with a single transmembrane domain. The extracellular domain (ECD) of both Notch receptors and Notch ligands contains numerous epidermal growth factor (EGF)-like repeats which are post-translationally modified by a variety of glycans. Inactivation of a subset of genes that encode glycosyltransferases which initiate and elongate these glycans inhibits Notch signaling. In the formation of developmental boundaries in Drosophila and mammals, in mouse T-cell and marginal zone B-cell development, and in co-culture Notch signaling assays, the regulation of Notch signaling by glycans is to date a cell-autonomous effect of the Notch-expressing cell. The regulation of Notch signaling by glycans represents a new paradigm of signal transduction. O-fucose glycans modulate the strength of Notch binding to DSL Notch ligands, while O-glucose glycans facilitate juxta-membrane cleavage of Notch, generating the substrate for intramembrane cleavage and Notch activation. Identifying precisely how the addition of particular sugars at specific locations on Notch modifies Notch signaling is a challenge for the future.
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U2 - 10.1016/S0070-2153(10)92004-8
DO - 10.1016/S0070-2153(10)92004-8
M3 - Article
C2 - 20816394
AN - SCOPUS:77956331145
SN - 0070-2153
VL - 92
SP - 131
EP - 164
JO - Current Topics in Developmental Biology
JF - Current Topics in Developmental Biology
IS - C
ER -