Biochemical characterization of the Drosophila axin protein.
In the Wnt/Wingless pathway, accumulation of beta-catenin/Armadillo protein is a key regulatory step. Vertebrate Axin is a negative regulator of Wnt signaling, promoting glycogen synthase kinase-3beta-mediated phosphorylation of beta-catenin and thereby destabilizing beta-catenin. Using Drosophila cell culture systems, we demonstrated that a Drosophila homolog of Axin (Daxin) inhibits Wingless-induced Armadillo accumulation and Drosophila T-cell factor-dependent transcription induced by Wingless, Dishevelled, and Armadillo. The carboxy-terminal portion of Daxin is not essential for the inhibitory activity, but a mutant only consisting of this portion behaves as a dominant-negative protein. Moreover, interactions between Daxin and Zeste-white 3, Armadillo, Dishevelled, protein phosphatase 2A and Daxin itself were shown, providing direct evidence that Daxin is a scaffold protein in the Wingless pathway.
Yanagawa
S
S
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan. syanagaw@virus.kyoto-u.ac.jp
Lee
J S
JS
Matsuda
Y
Y
Ishimoto
A
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051186:Armadillo Domain Proteins; D060466:Axin Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D038362:Glycogen Synthase Kinase 3; D006609:High Mobility Group Proteins / Q000378:metabolism; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics; D051155:Wnt1 Protein; D051176:beta Catenin
C495305:ARM protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D051186:Armadillo Domain Proteins; D060466:Axin Protein; C118000:Axn protein, Drosophila; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D019476:Insect Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; D051176:beta Catenin; C000606588:dsh protein, Drosophila; C115159:pan protein, Drosophila; C074622:wg protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2