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Vascular endothelial growth factor-induced elimination of the type 1 interferon receptor is required for efficient angiogenesis.
Zheng, Hui; Qian, Juan; Carbone, Christopher J; Leu, N Adrian; Baker, Darren P; Fuchs, Serge Y.
Afiliación
  • Zheng H; Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Blood ; 118(14): 4003-6, 2011 Oct 06.
Article en En | MEDLINE | ID: mdl-21832278
Angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and antagonized by type 1 interferons, including IFN-α/ß. On engaging their respective receptors (VEGFR2 and IFNAR), both stimuli activate protein kinase D2 (PKD2) and type 1 IFNs require PKD2 activation and recruitment to IFNAR1 to promote the phosphorylation-dependent ubiquitination, down-regulation, and degradation of the cognate receptor chain, IFNAR1. Data reveal that PKD2 activity is dispensable for VEGF-stimulated down-regulation of VEGFR2. Remarkably, VEGF treatment promotes the recruitment of PKD2 to IFNAR1 as well as ensuing phosphorylation, ubiquitination, and degradation of IFNAR1. In cells exposed to VEGF, phosphorylation-dependent degradation of IFNAR1 leads to an inhibition of type 1 IFN signaling and is required for efficient VEGF-stimulated angiogenesis. Importance of this mechanism for proangiogenic or antiangiogenic responses in cells exposed to counteracting stimuli and the potential medical significance of this regulation are discussed.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Fisiológica / Factor A de Crecimiento Endotelial Vascular / Receptor de Interferón alfa y beta Límite: Animals / Humans Idioma: En Revista: Blood Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Fisiológica / Factor A de Crecimiento Endotelial Vascular / Receptor de Interferón alfa y beta Límite: Animals / Humans Idioma: En Revista: Blood Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos