In vivo regulation of glycogen synthase kinase 3β activity in neurons and brains
| Autor: | Taro Saito, Kanae Ando, Shinichiro Takahashi, Kyota Aoyagi, Ambika Krishnankutty, Akiko Asada, Mica Ohara-Imaizumi, Shin-ichi Hisanaga, Taeko Kimura, Koichi Ishiguro |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Science Biology Aminophenols Article Cell Line Diabetes Mellitus Experimental Maleimides 03 medical and health sciences 0302 clinical medicine GSK-3 Animals Protein phosphorylation Kinase activity Insulin-Like Growth Factor I Phosphorylation Protein kinase A GSK3B Protein Kinase Inhibitors MAPK14 Cerebral Cortex Neurons Mice Inbred ICR Multidisciplinary Glycogen Synthase Kinase 3 beta Autophosphorylation Brain 030104 developmental biology Biochemistry Medicine Female Lithium Chloride 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) |
| ISSN: | 2045-2322 |
| Popis: | Glycogen synthase kinase 3β (GSK3β) is a multifunctional protein kinase involved in many cellular activities including development, differentiation and diseases. GSK3β is thought to be constitutively activated by autophosphorylation at Tyr216 and inactivated by phosphorylation at Ser9. The GSK3β activity has previously been evaluated by inhibitory Ser9 phosphorylation, but it does not necessarily indicate the kinase activity itself. Here, we applied the Phos-tag SDS-PAGE technique to the analysis of GSK3β phosphoisotypes in cells and brains. There were three phosphoisotypes of GSK3β; double phosphorylation at Ser9 and Tyr216, single phosphorylation at Tyr216 and the nonphosphorylated isotype. Active GSK3β with phosphorylation at Tyr216 represented half or more of the total GSK3β in cultured cells. Although levels of phospho-Ser9 were increased by insulin treatment, Ser9 phosphorylation occurred only in a minor fraction of GSK3β. In mouse brains, GSK3β was principally in the active form with little Ser9 phosphorylation, and the phosphoisotypes of GSK3β changed depending on the regions of the brain, age, sex and disease conditions. These results indicate that the Phos-tag SDS-PAGE method provides a simple and appropriate measurement of active GSK3β in vivo, and the activity is regulated by the mechanism other than phosphorylation on Ser9. |
| Databáze: | OpenAIRE |
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