scholarly journals Adenomatous Polyposis Coli (APC) Regulates Multiple Signaling Pathways by Enhancing Glycogen Synthase Kinase-3 (GSK-3) Activity

2011 ◽  
Vol 287 (6) ◽  
pp. 3823-3832 ◽  
Author(s):  
Alexander J. Valvezan ◽  
Fang Zhang ◽  
J. Alan Diehl ◽  
Peter S. Klein
Keyword(s):  
Signaling Pathways ◽  
Adenomatous Polyposis Coli ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Multiple Signaling

scholarly journals Interaction of Dishevelled and XenopusAxin-Related Protein Is Required for Wnt Signal Transduction

2000 ◽  
Vol 20 (6) ◽  
pp. 2228-2238 ◽  
Author(s):  
Keiji Itoh ◽  
Alena Antipova ◽  
Marianne J. Ratcliffe ◽  
Sergei Sokol
Keyword(s):  
Signal Transduction ◽  
Adenomatous Polyposis Coli ◽  
Glycogen Synthase ◽  
Secreted Proteins ◽  
Glycogen Synthase Kinase 3 ◽  
Adenomatous Polyposis ◽  
Related Protein ◽  
Polyposis Coli ◽  
Animal Development ◽  
Wnt Signal

ABSTRACT Signaling by the Wnt family of secreted proteins plays an important role in animal development and is often misregulated in carcinogenesis. Wnt signal transduction is controlled by the rate of degradation of β-catenin by a complex of proteins including glycogen synthase kinase 3 (GSK3), adenomatous polyposis coli, and Axin. Dishevelled is required for Wnt signal transduction, and its activation results in stabilization of β-catenin. However, the biochemical events underlying this process remain largely unclear. Here we show thatXenopus Dishevelled (Xdsh) interacts with aXenopus Axin-related protein (XARP). This interaction depends on the presence of the Dishevelled-Axin (DIX) domains in both XARP and Xdsh. Moreover, the same domains are essential for signal transduction through Xdsh. Finally, our data point to a possible mechanism for signal transduction, in which Xdsh prevents β-catenin degradation by displacing GSK3 from its complex with XARP.

scholarly journals Glycogen Synthase Kinase-3 Is Required for EfficientDictyosteliumChemotaxis

2010 ◽  
Vol 21 (15) ◽  
pp. 2788-2796 ◽  
Author(s):  
Regina Teo ◽  
Kimberley J. Lewis ◽  
Josephine E. Forde ◽  
W. Jonathan Ryves ◽  
Jonathan V. Reddy ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Glycogen Synthase ◽  
Cell Aggregation ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cell Fate Determination ◽  
Cell Signaling Pathways

Glycogen synthase kinase-3 (GSK3) is a highly conserved protein kinase that is involved in several important cell signaling pathways and is associated with a range of medical conditions. Previous studies indicated a major role of the Dictyostelium homologue of GSK3 (gskA) in cell fate determination during morphogenesis of the fruiting body; however, transcriptomic and proteomic studies have suggested that GSK3 regulates gene expression much earlier during Dictyostelium development. To investigate a potential earlier role of GskA, we examined the effects of loss of gskA on cell aggregation. We find that cells lacking gskA exhibit poor chemotaxis toward cAMP and folate. Mutants fail to activate two important regulatory signaling pathways, mediated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and target of rapamycin complex 2 (TORC2), which in combination are required for chemotaxis and cAMP signaling. These results indicate that GskA is required during early stages of Dictyostelium development, in which it is necessary for both chemotaxis and cell signaling.

scholarly journals Adenomatous Polyposis Coli Protein Associates with C/EBP β and Increases Bacillus anthracis Edema Toxin-stimulated Gene Expression in Macrophages

2011 ◽  
Vol 286 (22) ◽  
pp. 19364-19372 ◽  
Author(s):  
Jason L. Larabee ◽  
Salika M. Shakir ◽  
Logan Hightower ◽  
Jimmy D. Ballard
Keyword(s):  
Gene Expression ◽  
Bacillus Anthracis ◽  
Adenomatous Polyposis Coli ◽  
Glycogen Synthase ◽  
Transcriptional Level ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Adenomatous Polyposis Coli Protein ◽  
Edema Toxin ◽  
Inducible Protein

The production of cAMP from Bacillus anthracis edema toxin (ET) activates gene expression in macrophages through a complex array of signaling pathways, most of which remain poorly defined. In this study, the tumor suppressor protein adenomatous polyposis coli (APC) was found to be important for the up-regulation of previously defined ET-stimulated genes (Vegfa, Ptgs2, Arg2, Cxcl2, Sdc1, and Cebpb). A reduction in the expression of these genes after ET exposure was observed when APC was disrupted in macrophages using siRNA or in bone marrow-derived macrophages obtained from C57BL/6J-ApcMin mice, which are heterozygous for a truncated form of APC. In line with this observation, ET increased the expression of APC at the transcriptional level, leading to increased amounts of APC in the nucleus. The mechanism utilized by APC to increase ET-induced gene expression was determined to depend on the ability of APC to interact with C/EBP β, which is a transcription factor activated by cAMP. Coimmunoprecipitation experiments found that APC associated with C/EBP β and that levels of this complex increase after ET exposure. A further connection was uncovered when silencing APC was determined to reduce the ET-induced phosphorylation of C/EBP β at Thr-188. This ET-mediated phosphorylation of C/EBP β was blocked by glycogen synthase kinase 3 (GSK-3) inhibitors, suggesting that GSK-3 is involved in the activation of C/EBP β and supporting the idea of APC helping direct interactions between GSK-3 and C/EBP β. These results indicate that ET stimulates gene expression by promoting the formation of an inducible protein complex consisting of APC and C/EBP β.

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