Calcineurin dephosphorylates glycogen synthase kinase-3 beta at serine-9 in neuroblast-derived cells |
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Authors: | Yeni Kim&dagger ,Yun-Il Lee,MiRan Seo,So-Young Kim,Ji-Eun Lee,Hong-Duk Youn,Yong-Sik Kim&Dagger , Yong-Sung Juhnn |
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Affiliation: | Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Mental Health, Seoul National Hospital, Seoul, Korea; Department of Psychiatry and Behavioral Science and Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Korea |
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Abstract: | This study examined the role of calcineurin, a major calcium-dependent protein phosphatase, in dephosphorylating Ser-9 and activating glycogen synthase kinase-3β (GSK-3β). Treatment with calcineurin inhibitors increased phosphorylation of GSK-3β at Ser-9 in SH-SY5Y human neuroblastoma cells. The over-expression of a constitutively active calcineurin mutant, calcineurin A beta (1–401), led to a significant decrease in phosphorylation at Ser-9, an increase in the activity of GSK-3β, and an increase in the phosphorylation of tau. Km of calcineurin for a GSK-3β phosphopeptide was 469.3 μM, and specific activity of calcineurin was 15.2 nmol/min/mg. In addition, calcineurin and GSK-3β were co-immunoprecipitated in neuron-derived cells and brain tissues, and calcineurin formed a complex only with dephosphorylated GSK-3β. We conclude that in vitro, calcineurin can dephosphorylate GSK-3β at Ser-9 and form a stable complex with GSK-3β, suggesting the possibility that calcineurin regulates the dephosphorylation and activation of GSK-3β in vivo . |
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Keywords: | brain calcineurin dephosphorylation glycogen synthase kinase-3β neuron-derived cells |
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