| Literature DB >> 21220102 |
Tsutomu Sasaki1, Hiroshi Takemori, Yoshiki Yagita, Yasukazu Terasaki, Tatsuya Uebi, Nanao Horike, Hiroaki Takagi, Teruo Susumu, Hiroshi Teraoka, Ken-Ichi Kusano, Osamu Hatano, Naoki Oyama, Yukio Sugiyama, Saburo Sakoda, Kazuo Kitagawa.
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. Copyright ÂEntities:
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Year: 2011 PMID： 21220102 DOI： 10.1016/j.neuron.2010.12.004
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173