SIK2 is a key regulator for neuronal survival after ischemia via TORC1-CREB.

Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Neuron (Impact Factor: 15.98). 01/2011; 69(1):106-19. DOI: 10.1016/j.neuron.2010.12.004
Source: PubMed

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.

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Available from: Yoshiki Yagita, Jul 08, 2015
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