Inhibition of the Wnt signaling pathway by Idax, a novel Dvl-binding protein.
In attempting to clarify the roles of Dvl in the Wnt signaling pathway, we identified a novel protein which binds to the PDZ domain of Dvl and named it Idax (for inhibition of the Dvl and Axin complex). Idax and Axin competed with each other for the binding to Dvl. Immunocytochemical analyses showed that Idax was localized to the same place as Dvl in cells and that expression of Axin inhibited the colocalization of Dvl and Idax. Further, Wnt-induced accumulation of beta-catenin and activation of T-cell factor in mammalian cells were suppressed by expression of Idax. Expression of Idax in Xenopus embryos induced ventralization with a reduction in the expression of siamois, a Wnt-inducible gene. Idax inhibited Wnt- and Dvl- but not beta-catenin-induced axis duplication. It is known that Dvl is a positive regulator in the Wnt signaling pathway and that the PDZ domain is important for this activity. Therefore, these results suggest that Idax functions as a negative regulator of the Wnt signaling pathway by directly binding to the PDZ domain of Dvl.
Hino
S
S
Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Kishida
S
S
Michiue
T
T
Fukui
A
A
Sakamoto
I
I
Takada
S
S
Asashima
M
M
Kikuchi
A
A
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D060466:Axin Protein; D019521:Body Patterning; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C495266:CTNNB1 protein, Xenopus; C418221:CXXC4 protein, human; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; C485963:Cxxc4 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C093133:SIA1 protein, Xenopus; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin