当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.

The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.

Abstract：

:Mechanisms by which the extracellular domain of Notch1 controls Notch1 signaling are not well defined. Here, we show that the O-fucose glycan in the Notch1 ligand-binding domain regulates the strength of Notch1 signaling during embryogenesis, postweaning growth, and T cell development in the mouse. Heterozygotes carrying a Notch1(12f) allele and an inactive Notch1 allele die at approximately embryonic day (E)12 with a typical Notch1 null phenotype. Homozygous Notch1(12f/12f) mice are viable and fertile but grow somewhat more slowly than littermates after weaning. Notch1(12f/12f) thymocytes bind less Delta1 and exhibit reduced Notch1 signaling. The number of double-positive (DP) and single-positive (SP) T cells are decreased in Notch1(12f/12f) thymus, and DP T cells are more apoptotic. By contrast, proportionately more SP cells have matured, and SP-to-DP ratios are increased in mutant thymus. Thus, the O-fucose glycan in EGF12 of mouse Notch1 is required for optimal Notch1 signaling and T cell development in mammals.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Ge C,Stanley P

doi

10.1073/pnas.0702846105

subject

Has Abstract

pub_date

2008-02-05 00:00:00

pages

1539-44

issue

5

eissn

0027-8424

issn

1091-6490

pii

0702846105

journal_volume

105

pub_type

杂志文章

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