Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription.
The Dishevelled (Dvl) gene family encodes cytoplasmic proteins that are necessary for Wnt signal transduction. Utilizing the yeast two-hybrid system, we identified protein phosphatase 2Calpha (PP2C) as a Dvl-PDZ domain-interacting protein. PP2C exists in a complex with Dvl, beta-catenin, and Axin, a negative regulator of Wnt signaling. In a Wnt-responsive LEF-1 reporter gene assay, expression of PP2C activates transcription and also elicits a synergistic response with beta-catenin and Wnt-1. In addition, PP2C expression relieves Axin-mediated repression of LEF-1-dependent transcription. PP2C utilizes Axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that PP2C is a positive regulator of Wnt signal transduction and mediates its effects through the dephosphorylation of Axin.
Strovel
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Division of Human Genetics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Wu
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D
Sussman
D J
DJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D051821:Lymphoid Enhancer-Binding Factor 1; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D010750:Phosphoproteins; D011506:Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C