TY - JOUR
T1 - A mutation in EGF repeat-8 of notch discriminates between serrate/jagged and delta family ligands
AU - Yamamoto, Shinya
AU - Charng, Wu Lin
AU - Rana, Nadia A.
AU - Kakuda, Shinako
AU - Jaiswal, Manish
AU - Bayat, Vafa
AU - Xiong, Bo
AU - Zhang, Ke
AU - Sandoval, Hector
AU - David, Gabriela
AU - Wang, Hao
AU - Haltiwanger, Robert S.
AU - Bellen, Hugo J.
PY - 2012/11/30
Y1 - 2012/11/30
N2 - Notch signaling affects many developmental and cellular processes and has been implicated in congenital disorders, stroke, and numerous cancers. The Notch receptor binds its ligands Delta and Serrate and is able to discriminate between them in different contexts. However, the specific domains in Notch responsible for this selectivity are poorly defined. Through genetic screens in Drosophila, we isolated a mutation, Notchjigsaw, that affects Serrate- but not Delta-dependent signaling. Notchjigsaw carries a missense mutation in epidermal growth factor repeat-8 (EGFr-8) and is defective in Serrate binding. A homologous point mutation in mammalian Notch2 also exhibits defects in signaling of a mammalian Serrate homolog, Jagged1. Hence, an evolutionarily conserved valine in EGFr-8 is essential for ligand selectivity and provides a molecular handle to study numerous Notch-dependent signaling events.
AB - Notch signaling affects many developmental and cellular processes and has been implicated in congenital disorders, stroke, and numerous cancers. The Notch receptor binds its ligands Delta and Serrate and is able to discriminate between them in different contexts. However, the specific domains in Notch responsible for this selectivity are poorly defined. Through genetic screens in Drosophila, we isolated a mutation, Notchjigsaw, that affects Serrate- but not Delta-dependent signaling. Notchjigsaw carries a missense mutation in epidermal growth factor repeat-8 (EGFr-8) and is defective in Serrate binding. A homologous point mutation in mammalian Notch2 also exhibits defects in signaling of a mammalian Serrate homolog, Jagged1. Hence, an evolutionarily conserved valine in EGFr-8 is essential for ligand selectivity and provides a molecular handle to study numerous Notch-dependent signaling events.
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U2 - 10.1126/science.1228745
DO - 10.1126/science.1228745
M3 - Article
C2 - 23197537
AN - SCOPUS:84870224298
SN - 0036-8075
VL - 338
SP - 1229
EP - 1232
JO - Science
JF - Science
IS - 6111
ER -