The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5
Experimental & Molecular Medicine
;
: e200-2015.
Artículo
en Inglés
| WPRIM
| ID: wpr-228163
ABSTRACT
Endocytosis is differentially regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) and phospholipase D (PLD). However, the relationship between HIF-1alpha and PLD in endocytosis is unknown. HIF-1alpha is degraded through the prolyl hydroxylase (PHD)/von Hippel-Lindau (VHL) ubiquitination pathway in an oxygen-dependent manner. Here, we show that PLD1 recovers the decrease in epidermal growth factor receptor (EGFR) endocytosis induced by HIF-1alpha independent of lipase activity via the Rab5-mediated endosome fusion pathway. EGF-induced interaction of PLD1 with HIF-1alpha, PHD and VHL may contribute to EGFR endocytosis. The pleckstrin homology domain (PH) of PLD1 itself promotes degradation of HIF-1alpha, then accelerates EGFR endocytosis via upregulation of rabaptin-5 and suppresses tumor progression. These findings reveal a novel role of the PLD1-PH domain as a positive regulator of endocytosis and provide a link between PLD1 and HIF-1alpha in the EGFR endocytosis pathway.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fosfolipasa D
/
Fosfoproteínas
/
Proteínas Sanguíneas
/
Transducción de Señal
/
Regulación hacia Arriba
/
Estructura Terciaria de Proteína
/
Células HT29
/
Proteínas de Unión al GTP rab5
/
Proteínas de Transporte Vesicular
/
Endocitosis
Límite:
Animales
/
Femenino
/
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2015
Tipo del documento:
Artículo
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