title: Ser9-phosphorylated GSK3β induced by 14-3-3ζ actively antagonizes cell apoptosis in a NF-κB dependent manner.
abstract: The activity of glycogen synthase kinase beta (GSK3β) is mainly regulated by its Ser9 phosphorylation. It has been believed for a long time that Ser9 phosphorylation regulates the functions of GSK3β through inhibition of its kinase activity. In this study, we have confirmed the interaction of Ser9-phosphorylated GSK3β with 14-3-3ζ by using GST pull-down assays. We show that 14-3-3ζ enhances Ser9 phosphorylation of GSK3β by PKC. Surprisingly, using a NF-κB luciferase reporter system, we find that Ser9-phosphorylation of GSK3β promoted by 14-3-3ζ is critical for the activation of NF-κB pathway, which may thwart the pro-apoptotic activity of GSK3β. Inhibition of either NF-κB or GSK3β significantly abolishes the anti-apoptotic effect of 14-3-3ζ and Ser9-phosphorylated GSK3β, suggesting that Ser9-phosphorylated GSK3β actively antagonizes cell apoptosis in a NF-κB dependent manner.
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Gao
authors.forename: Yujiao
authors.initials: Y
authors.lastname: He
authors.forename: Ling-Mei
authors.initials: LM
authors.lastname: Gao
authors.forename: Junxia
authors.initials: J
authors.lastname: Feng
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xie
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Langxia
authors.initials: L
authors.lastname: Liu
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048948:14-3-3 Proteins; D016328:NF-kappa B; D010768:Phosphoserine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3
keywords: 14-3-3ζ; GSK3β; Ser9 phosphorylation; apoptose; apoptosis; interaction; phosphorylation sur la Ser9