title: Astrocytic phosphorylation of PDK1 on Tyr9 following an excitotoxic lesion in the mouse hippocampus.
abstract: 3-phosphoinositide-dependent kinase-1 (PDK1) is suggested to play important roles in the regulation of synaptic plasticity and neuronal cell survival in the mature CNS. Although few studies have investigated the roles of PDK1, little is known about PDK1 changes in glial cells under neuropathological conditions. In current report, phosphorylation of PDK1 was monitored specially on tyrosine residues, following the induction of an excitotoxic lesion in rat brain by using kainic acid administration. In injured hippocampal CA3 region, Tyr9 phosphorylation of PDK1 was increased from 4h until 3 day post-injection. Double immunohistochemistry further evaluated that these phosphorylated forms of PDK1 were localized in astrocytes not other cells. Overexpression of unphosphorylatable mutant, PDK1-Y9F leads to inhibit Protein kinase B (PKB/Akt) activation and cAMP responsive element binding protein (CREB) phosphorylation. In conclusion, our results suggested for the first time that tyrosine phosphorylation of PDK1 is required for PKB and CREB activation in KA-mediated excitotoxic lesion in mouse brain.
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon, 301-747, South Korea.
authors: Jisoo
authors: J
authors: Park
authors: Kisang
authors: K
authors: Kwon
authors: Seon-Hwan
authors: SH
authors: Kim
authors: Min-Hee
authors: MH
authors: Yi
authors: Enji
authors: E
authors: Zhang
authors: Gyeyeong
authors: G
authors: Kong
authors: Dong Woon
authors: DW
authors: Kim
authors: Jongsun
authors: J
authors: Park
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*
chemical_list: D019000:Phosphotyrosine; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578564:Pdpk1 protein, mouse; D007608:Kainic Acid
keywords: Astrocyte; Cell signaling; Epilepsy; Neurodegerative disease; PDK1; Phosphorylation