Regulation of vascular endothelial growth factor receptor function in angiogenesis by numb and numb-like.
Arterioscler Thromb Vasc Biol
; 35(8): 1815-25, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26069237
ABSTRACT
OBJECTIVE:
Vascular endothelial growth factor (VEGF) signaling is a major regulator of physiological and pathological angiogenesis. VEGF receptor activity is strongly controlled by endocytosis, which can terminate or enhance signal transduction in the angiogenic endothelium, but the exact molecular regulation of these processes remains incompletely understood. We have therefore examined the function of Numb family clathrin-associated sorting proteins in angiogenesis. APPROACH ANDRESULTS:
We show that Numb proteins are expressed by endothelial cells during retinal angiogenesis in mice. Inducible inactivation of the Numb/Numbl genes in the postnatal endothelium led to impaired vessel growth, reduced endothelial proliferation and sprouting, and decreased VEGF receptor activation. Biochemistry and cell biology experiments established that Numb can interact with VEGFR2 and VEGFR3 and controls VEGF receptor activation in response to ligand stimulation. Experiments in cultured endothelial cells showed that Numb proteins counteract VEGF receptor degradation and promote VEGFR2 recycling back to the plasma membrane.CONCLUSIONS:
Numb proteins control VEGF receptor endocytosis, signaling, and recycling in endothelial cells, which promotes the angiogenic growth of blood vessels.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neovascularização Retiniana
/
Neovascularização Fisiológica
/
Receptores de Fatores de Crescimento do Endotélio Vascular
/
Células Endoteliais
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Membrana
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article