scholarly journals DictyosteliumDifferentiation-inducing Factor-3 Activates Glycogen Synthase Kinase-3β and Degrades Cyclin D1 in Mammalian Cells

2003 ◽  
Vol 278 (11) ◽  
pp. 9663-9670 ◽  
Author(s):  
Fumi Takahashi-Yanaga ◽  
Yoji Taba ◽  
Yoshikazu Miwa ◽  
Yuzuru Kubohara ◽  
Yutaka Watanabe ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mammalian Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Glycogen synthase kinase 3β and cyclin D1 expression in cervical carcinogenesis

2016 ◽  
Vol 59 (6) ◽  
pp. 470 ◽  
Author(s):  
Hyunsoo Park ◽  
Myunghwa Lee ◽  
Dae Woon Kim ◽  
Seo Yoo Hong ◽  
Hojung Lee
Keyword(s):  
Cyclin D1 ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Cervical Carcinogenesis ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Laforin Negatively Regulates Cell Cycle Progression through Glycogen Synthase Kinase 3β-Dependent Mechanisms

2008 ◽  
Vol 28 (23) ◽  
pp. 7236-7244 ◽  
Author(s):  
Runhua Liu ◽  
Lizhong Wang ◽  
Chong Chen ◽  
Yan Liu ◽  
Penghui Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Tumor Suppression ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Cycle Progression ◽  
Gsk 3Β

ABSTRACT Glycogen synthase kinase 3β (GSK-3β) represses cell cycle progression by directly phosphorylating cyclin D1 and indirectly regulating cyclin D1 transcription by inhibiting Wnt signaling. Recently, we reported that the Epm2a-encoded laforin is a GSK-3β phosphatase and a tumor suppressor. The cellular mechanism for its tumor suppression remains unknown. Using ex vivo thymocytes and primary embryonic fibroblasts from Epm2a −/− mice, we show here a general function of laforin in the cell cycle regulation and repression of cyclin D1 expression. Moreover, targeted mutation of Epm2a increased the phosphorylation of Ser9 on GSK-3β while having no effect on the phosphorylation of Ser21 on GSK-3α. In the GSK-3β+/+ but not the GSK-3β−/− cells, Epm2a small interfering RNA significantly enhanced cell growth. Consistent with an increased level of cyclin D1, the phosphorylation of retinoblastoma protein (Rb) and the levels of Rb-E2F-regulated genes cyclin A, cyclin E, MCM3, and PCNA are also elevated. Inhibitors of GSK-3β selectively increased the cell growth of Epm2a +/+ but not of Epm2a −/− cells. Taken together, our data demonstrate that laforin is a selective phosphatase for GSK-3β and regulates cell cycle progression by GSK-3β-dependent mechanisms. These data provide a cellular basis for the tumor suppression activity of laforin.

scholarly journals Noxious Stimulation Attenuates Ketamine-induced Neuroapoptosis in the Developing Rat Brain

2012 ◽  
Vol 117 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Jia-Ren Liu ◽  
Qian Liu ◽  
Jing Li ◽  
Chongwha Baek ◽  
Xiao Hui Han ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Glycogen Synthase Kinase ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Noxious Stimulation ◽  
Glycogen Synthase Kinase 3Β ◽  
Rat Pups

Background Ketamine induces neuroapoptosis in neonatal rodents. However, these experimental paradigms were performed without concurrent noxious stimulation, a condition that does not reflect the interaction of anesthesia and surgical stimulation. Noxious stimulation with and without concurrent analgesic drugs has been shown to have divergent patterns of neuronal activation and cell death. We hypothesized that concurrent noxious stimulation would attenuate ketamine-induced caspase-3 activation. Methods Postnatal day 7 Sprague-Dawley rat pups were randomized to a 6-h exposure to ketamine with and without peripheral noxious stimulation by intraplantar injection of complete Freund's adjuvant. A cohort of naïve rat pups with and without complete Freund's adjuvant injections served as control subjects. Neuroapoptosis was measured by cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining. In order to determine if concurrent noxious simulation altered the expression of cell survival and cell cycle proteins, levels of protein kinase B and glycogen synthase kinase-3β and cyclin D1 were measured. Results Ketamine induced a significant increase in cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining with increases in cyclin D1 levels. Concurrent noxious stimulation with ketamine attenuated caspase-3 activation and maintained cyclin D1 levels. Phosphorylation of protein kinase B and glycogen synthase kinase-3β was not definitively altered under these conditions. Conclusion The administration of ketamine with concurrent noxious stimulation results in the attenuation of the neuroapoptotic response. These findings suggest that concurrent surgery and procedural pain attenuates ketamine-induced neuroapoptosis.

Phosphorylation of tau by glycogen synthase kinase 3β in intact mammalian cells influences the stability of microtubules

2001 ◽  
Vol 312 (3) ◽  
pp. 141-144 ◽  
Author(s):  
Huachun Sang ◽  
Zhonghua Lu ◽  
Yulong Li ◽  
Binggen Ru ◽  
Wenqing Wang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
The Stability

scholarly journals The Janus Kinase 2 Is Required for Expression and Nuclear Accumulation of Cyclin D1 in Proliferating Mammary Epithelial Cells

2007 ◽  
Vol 21 (8) ◽  
pp. 1877-1892 ◽  
Author(s):  
Kazuhito Sakamoto ◽  
Bradley A. Creamer ◽  
Aleata A. Triplett ◽  
Kay-Uwe Wagner
Keyword(s):  
Epithelial Cells ◽  
Cyclin D1 ◽  
Nuclear Export ◽  
Mammary Epithelial Cells ◽  
Glycogen Synthase ◽  
Mammary Epithelial ◽  
Janus Kinase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Janus Kinase 2

Abstract Using a conditional knockout approach, we previously demonstrated that the Janus kinase 2 (Jak2) is crucial for prolactin (PRL) signaling and normal mammary gland development. PRL is suggested to synchronously activate multiple signaling cascades that emerge on the PRL receptor (PRLR). This study demonstrates that Jak2 is essential for the activation of the signal transducer and activator of transcription 5 (Stat5) and expression of Cish (cytokine-inducible SH2-containing protein), a Stat5-responsive negative regulator of Jak/Stat signaling. However, Jak2 is dispensable for the PRL-induced activation of c-Src, focal adhesion kinase, and the MAPK pathway. Despite activation of these kinases that are commonly associated with proliferative responses, the ablation of Jak2 reduces the multiplication of immortalized mammary epithelial cells (MECs). Our studies show that signaling through Jak2 controls not only the transcriptional activation of the Cyclin D1 gene, but, more importantly, it regulates the accumulation of the Cyclin D1 protein in the nucleus by altering the activity of signal transducers that mediate the phosphorylation and subsequent nuclear export of Cyclin D1. In particular, the levels of activated Akt (protein kinase B) and inactive glycogen synthase kinase-3β (i.e. a kinase that regulates the nuclear export and degradation of Cyclin D1) are reduced in MECs lacking Jak2. The proliferation of Jak2-deficient MECs can be rescued by expressing of a mutant form of Cyclin D1 that cannot be phosphorylated by glycogen synthase kinase-3β and therefore constitutively resides in the nucleus. Besides discriminating Jak2-dependent and Jak2-independent signaling events emerging from the PRLR, our observations provide a possible mechanism for phenotypic similarities between Cyclin D1 knockouts and females lacking individual members of the PRLR signaling cascade, in particular the PRLR, Jak2, and Stat5.

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