SIK2 is a key regulator for neuronal survival after ischemia via TORC1-CREB.
Neuron
; 69(1): 106-19, 2011 Jan 13.
Article
em En
| MEDLINE
| ID: mdl-21220102
ABSTRACT
The cAMP responsive element-binding protein (CREB) functions in a broad array of biological and pathophysiological processes. We found that salt-inducible kinase 2 (SIK2) was abundantly expressed in neurons and suppressed CREB-mediated gene expression after oxygen-glucose deprivation (OGD). OGD induced the degradation of SIK2 protein concomitantly with the dephosphorylation of the CREB-specific coactivator transducer of regulated CREB activity 1 (TORC1), resulting in the activation of CREB and its downstream gene targets. Ca(2+)/calmodulin-dependent protein kinase I/IV are capable of phosphorylating SIK2 at Thr484, resulting in SIK2 degradation in cortical neurons. Neuronal survival after OGD was significantly increased in neurons isolated from sik2(-/-) mice, and ischemic neuronal injury was significantly reduced in the brains of sik2(-)(/-) mice subjected to transient focal ischemia. These findings suggest that SIK2 plays critical roles in neuronal survival, is modulated by CaMK I/IV, and regulates CREB via TORC1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosforilação
/
Fatores de Transcrição
/
Hipóxia Celular
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Sobrevivência Celular
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Proteínas Serina-Treonina Quinases
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Proteína de Ligação a CREB
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article