Ape1/Ref-1 Stimulates GDNF/GFR alpha1-mediated Downstream Signaling and Neuroblastoma Proliferation
The Korean Journal of Physiology and Pharmacology
; : 349-356, 2009.
Article
em En
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| ID: wpr-727513
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WPRO
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.
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Assunto principal:
RNA
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Transdução de Sinais
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Regulação para Baixo
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Neuroglia
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RNA Interferente Pequeno
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Proliferação de Células
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Fator Neurotrófico Derivado de Linhagem de Célula Glial
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Neuroblastoma
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2009
Tipo de documento:
Article