The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis.
Cell
; 137(6): 1124-35, 2009 Jun 12.
Article
em En
| MEDLINE
| ID: mdl-19524514
ABSTRACT
The Notch pathway is a highly conserved signaling system that controls a diversity of growth, differentiation, and patterning processes. In growing blood vessels, sprouting of endothelial tip cells is inhibited by Notch signaling, which is activated by binding of the Notch receptor to its ligand Delta-like 4 (Dll4). Here, we show that the Notch ligand Jagged1 is a potent proangiogenic regulator in mice that antagonizes Dll4-Notch signaling in cells expressing Fringe family glycosyltransferases. Upon glycosylation of Notch, Dll4-Notch signaling is enhanced, whereas Jagged1 has weak signaling capacity and competes with Dll4. Our findings establish that the equilibrium between two Notch ligands with distinct spatial expression patterns and opposing functional roles regulates angiogenesis, a mechanism that might also apply to other Notch-controlled biological processes.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vasos Sanguíneos
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Proteínas de Ligação ao Cálcio
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Neovascularização Fisiológica
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Peptídeos e Proteínas de Sinalização Intercelular
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido