The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis.
Cell Mol Life Sci
; 75(15): 2813-2826, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29428965
ABSTRACT
Presenilin-1 (PS1) gene encodes the catalytic component of γ-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and tube formation, stimulates the formation of angiogenic complexes that include VE-cadherin, Raf-1 and Rok-α, and increases MLC2 phosphorylation. These functions are mediated by the PDZ-binding domain of efnB2. Acute downregulation of PS1 or inhibition of γ-secretase inhibits the angiogenic functions of EphB4 while absence of PS1 decreases the VE-cadherin angiogenic complexes of mouse brain. Our data reveal a mechanism by which PS1/γ-secretase regulates efnB2/EphB4 mediated angiogenesis.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos
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Antígenos CD
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Caderinas
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Neovascularização Fisiológica
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Células Endoteliais
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Secretases da Proteína Precursora do Amiloide
Limite:
Animals
Idioma:
En
Revista:
Cell Mol Life Sci
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos