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BMC Dev Biol. 2008 Jan 21;8:4. doi: 10.1186/1471-213X-8-4.

Competition between Delta and the Abruptex domain of Notch.

Author information

1
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. zpei@aecom.yu.edu

Abstract

BACKGROUND:

Extracellular domains of the Notch family of signalling receptors contain many EGF repeat domains, as do their major ligands. Some EGF repeats are modified by O-fucosylation, and most have no identified role in ligand binding.

RESULTS:

Using a binding assay with purified proteins in vitro, it was determined that, in addition to binding to Delta, the ligand binding region of Notch bound to EGF repeats 22-27 of Notch, but not to other EGF repeat regions of Notch. EGF repeats 22-27 of Drosophila Notch overlap the genetically-defined 'Abruptex' region, and competed with Delta for binding to proteins containing the ligand-binding domain. Delta differed from the Abruptex domain in showing markedly enhanced binding at acid pH. Both Delta and the Abruptex region are heavily modified by protein O-fucosylation, but the split mutation of Drosophila Notch, which affects O-fucosylation of EGF repeat 14, did not affect binding of Notch to either Delta or the Abruptex region.

CONCLUSION:

The Abruptex region may serve as a barrier to Notch activation by competing for the ligand-binding domain of Notch.

PMID:
18208612
PMCID:
PMC2267168
DOI:
10.1186/1471-213X-8-4
[Indexed for MEDLINE]
Free PMC Article

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