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Citation
Yamamoto, S., Charng, W.L., Rana, N.A., Kakuda, S., Jaiswal, M., Bayat, V., Xiong, B., Zhang, K., Sandoval, H., David, G., Wang, H., Haltiwanger, R.S., Bellen, H.J. (2012). A Mutation in EGF Repeat-8 of Notch Discriminates Between Serrate/Jagged and Delta Family Ligands.  Science 338(6111): 1229--1232.
FlyBase ID
FBrf0220110
Publication Type
Research paper
Abstract

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, Notch(jigsaw), that affects Serrate- but not Delta-dependent signaling. Notch(jigsaw) 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.

PubMed ID
PubMed Central ID
PMC3663443 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Science
    Title
    Science
    Publication Year
    1895-
    ISBN/ISSN
    0036-8075
    Data From Reference
    Alleles (2)
    Genes (8)
    Physical Interactions (2)
    Cell Lines (1)
    Insertions (1)