Ape1/Ref-1 Stimulates GDNF/GFR alpha1-mediated Downstream Signaling and Neuroblastoma Proliferation
The Korean Journal of Physiology and Pharmacology
;
: 349-356, 2009.
Artículo
en Inglés
| WPRIM
| ID: wpr-727513
ABSTRACT
We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor alpha1 (GFR alpha1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRalpha1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR alpha1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRalpha1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR alpha1-specific RNA experiments demonstrated that the downregulation of GFR alpha1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC gamma-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR alpha signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
ARN
/
Transducción de Señal
/
Regulación hacia Abajo
/
Neuroglía
/
ARN Interferente Pequeño
/
Proliferación Celular
/
Factor Neurotrófico Derivado de la Línea Celular Glial
/
Neuroblastoma
/
Neuronas
Límite:
Animales
Idioma:
Inglés
Revista:
The Korean Journal of Physiology and Pharmacology
Año:
2009
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS